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  • 151. Malmström, H
    et al.
    Zackrisson, Anna Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Hur påverkar amifostin topotecan vid samtidig administrering. En randomiserad fas II och farmakokinetisk studie2000Inngår i: Läkarstämman,2000, Stockholm: Svenska läkaresällskapet , 2000Konferansepaper (Annet vitenskapelig)
  • 152. Malmström, M
    et al.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Carlsson, C
    Schmekel, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    No effect of chinese acupuncture on isocapnic hyperventilation with cold air in asthmatics, measured with impulse oscillometry.2002Inngår i: Acupuncture in Medicine, ISSN 0964-5284, Vol. 20, s. 66-73Artikkel i tidsskrift (Fagfellevurdert)
  • 153. Masquelier, M
    et al.
    Gunars, T
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Pålsson, M
    Amolins, A
    Plotniece, M
    Plotniece, A
    Makarova, N
    Vitols, S
    Plasma stability and cytotoxicity of lipophilic daunorubicin derivatives incorporated into low density lipoproteins2000Inngår i: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 35, nr 4, s. 429-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The selective targeting of antineoplastic drugs to tumours by incorporation in low density lipoproteins (LDL) is an attractive possibility if the drug-LDL complex remains stable in the circulation and is taken up by the tumour. In previous studies we have shown that vincristine- and N- trifluoroacetyladriamycin-14-valerate-LDL complexes were unstable in vivo. We synthesized five N-substituted lipophilic derivatives of daunorubicin and studied their incorporation into LDL. Three out of five daunorubicin derivatives incorporated successfully into LDL. In vitro these complexes were more cytotoxic towards LDL receptor positive Chinese hamster ovary cells than LDL receptor negative cells. Non-specific cytotoxicity was explained by slow dissociation of the drug-LDL complex in plasma. Our results underline the importance of careful studies of plasma stability when investigating lipoproteins and other carriers in drug targeting.

  • 154.
    Masquelier, Michéle
    et al.
    Karolinska, Stockholm.
    Lundgren, Bo
    Finland.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Vitols, Sigurd
    Karolinska, Stockholm.
    Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: Studies in human leukemic cells2006Inngår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 30, nr 2, s. 136-144Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells. Lipid-based formulations, such as liposomes or microemulsions are promising alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin-14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their cytotoxic activities towards leukemic cell lines using as references DNR and melphalan. The incorporation of AD32 into LDL or emulsion resulted in complexes with poor cytotoxicity. WB4291-LDL and WB4291-emulsion exerted, on the other hand, promising cytotoxic effects towards parental and resistant K562 and HL60 cell lines. © 2005 Elsevier Ltd. All rights reserved.

  • 155.
    Molander, L
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hansson, A
    Lunell, E
    Alainentalo, L
    Hoffman, Mikael
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Larsson, Rutger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Njurmedicinska kliniken US.
    Pharmacokinetics of nicotine in kidney failure2000Inngår i: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 68, nr 3, s. 250-260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Smoking is an important risk factor for cardiovascular and cerebrovascular complications in patients with chronic kidney failure. Very high plasma nicotine concentrations have been reported in patients with severe kidney failure, indicating that the disposition of nicotine in these patients may be different. The purpose of this study was to assess the pharmacokinetics of intravenously administered nicotine in healthy subjects and in patients with kidney failure. Methods: Nine healthy subjects (glomerular filtration rare [GFR], 84 to 143 mL/min/1.73 m2), four patients with mild kidney failure (GFR, 63 to 73 mL/min/1.73 m2), five patients with moderate kidney failure (GFR, 18 to 36 mL/min/1.73 m2), and six patients with severe kidney failure (GFR, 1 to 10 mL/min/1.73 m2) were recruited. Three patients were treated with continuous ambulatory peritoneal dialysis. An intravenous infusion of nicotine (0.028 mg/kg) was given for 10 minutes. Nicotine and cotinine concentrations were measured in plasma, urine, and peritoneal dialysate from 0 to 24 hours after start of infusion Results: There were significant correlations between GFR and total clearance, nonrenal and renal clearance of nicotine, area under the plasma concentration-time curve extrapolated to infinity, terminal elevation half-life, and mean residence time. Nonrenal clearance was 1303 mL/min and 661 mL/min in healthy subjects and patients with severe kidney failure, respectively. Only 1% to 2% of the nicotine dose was excreted unchanged in a 24-hour collection of peritoneal dialysate. The elimination of cotinine was also decreased in patients with kidney failure. Conclusion: Progressive kidney failure is associated with a gradual decrease of renal and nonrenal elimination of nicotine.

  • 156.
    Månsson, Emma
    et al.
    Division of Clinical Pharmacology, Department of Medicine, Karolinska Hospital, Stockholm.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Klas
    Department of Clinical Microbiology, Karolinska Hospital, Stockholm.
    Islam, Quamrul
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Staffan
    Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Biomedical Center, Uppsala.
    Albertioni, Freidoun
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    On the mechanism of 9-ß-D-arabinofuroanosylguanine resistance in human leukemic cellsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The present study was undertaken to elucidate the mechanism of resistance to a relatively new nucleoside, 9-ß-D-arabinofuranosylguanine (Ara-G), which is highly toxic to T-cell malignancies. In order to do this we generated two stable resistant cell lines, MOLT-4/AraG500 (100-fold resistant) and MOLT-4/Ara-G900 (180-fold resistant). The presumed limiting step in the activation of Ara-G is catalyzed by both deoxycytidine kinase (dCK) and the mitochondrial deoxyguanosine kinase (dGK). Cross-resistance was noted to analogues such as cytosine arabinoside (Ara-C), cladribine, and fludarabine, but not to difluorodeoxycytidine. HPLC measurements of intracellular triphosphates of Ara-C and Ara-G showed that resistant cells generated significantly lower levels of metabolites. The activity of dGK (MOLT-4/AraG500, 79%, and MOLT-4/Ara-G900, 83%) and dCK (MOLT-4/Ara-G500, 54%, and MOLT- 4/Ara-G900, 73%), as well as protein and mRNA levels were significantly reduced in the resistant cell lines compared to the wild type. The resistant cells also showed decreased activity as well as decreased mRNA expression of the cytosolic 5'-nucleotidase (5'-NT), compared to the wild type. The reduced levels of enzyme activity in the resistant cells may be a consequence of reduced numbers of chromosomes carrying the genes for dGK, dCK and 5 'NT. Unexpectedly, the resistant cells showed higher activity of the mitochondrial enzyme thymidine kinase 2, probably resulting from down-regulation of dGK. No mutations were found in the dCK gene ofMOLT-4/Ara-G500 but in 2 of 13 clones ofMOLT-4/Ara-G900, we found two point mutations, one T to C and other A to G, which gave rise to changes in the amino acid sequence and affected the catalytic activity. The intracellular dNTP levels were determined and a nearly unchanged dCTP pool was observed in the resistant cells, while the other dNTP pools were significantly reduced compared to those in the wild type. These results show that altered activity of the deoxyribonucleoside kinases confer resistance to Ara-G in these cell lines.

  • 157.
    Nielsen, Niels Erik
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Malmstedt, J
    Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Öhman, K. P.
    Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet.
    Swahn, Eva
    Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease1999Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 59, nr 5, s. 325-334Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66% significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.

  • 158. Olsson, M
    et al.
    Annerbrink, K
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Hedner, J
    Eriksson, E
    Paroxetine influences respiration in rats: Implications for the treatment of panic disorder2004Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 14, nr 1, s. 29-37Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Since hyperventilation and shortness of breath are characteristic features of panic attacks, and since the attacks can be elicited by CO2 inhalation, an involvement of central or peripheral chemoreceptors in the pathophysiology of panic disorder has been suggested. Prompted by clinical reports suggesting that the susceptibility to spontaneous as well as CO 2-induced anxiety and hyperventilation is attenuated by serotonin reuptake inhibitors (SRIs), we undertook the present study in order to explore the possible effect of an SRI, paroxetine, on baseline respiration and CO 2-induced hyperventilation in freely moving Wistar rats. A significant increase in baseline respiratory rate was seen both after 5 and 15 weeks of treatment with paroxetine. CO2 exposure induced a dose-dependent increase in respiratory rate, but not tidal volume, in both paroxetine-treated rats and controls, this response was reduced after 15 weeks of paroxetine treatment, but not after 5 weeks of treatment. We suggest that an influence on the regulation of respiration may be of importance for the anti-panic effect of SRIs.

  • 159.
    Palle, Josefin
    et al.
    Uppsala.
    Frost, Britt-Marie
    Uppsala.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Gustafsson, Göran
    Stockholm.
    Hellebostad, Marit
    Oslo.
    Kanerva, Jukka
    Helsingfors.
    Schmiegelow, Kjeld
    Köpenhamn.
    Lönnerholm, Gudmar
    Uppsala.
    Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia2006Inngår i: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 17, nr 4, s. 385-392Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m. The median clearance in non-DS children, 0.6-1.8 years old (n=4) and 2.5-17.7 years old (n=33), was 446 and 538 ml/min/m, respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P=0.036, analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P=0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P=0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m, respectively (P=0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring. © 2006 Lippincott Williams & Wilkins.

  • 160.
    Persson, Karin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Säfholm, A C E
    Andersson, Rolf
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Glyceryl trinitrate-induced angiotensin-converting enzyme (ACE) inhibition in healthy volunteers is dependent on ACE genotype2005Inngår i: Canadian Journal of Physiology and Pharmacology, ISSN 0008-4212, E-ISSN 1205-7541, Vol. 83, nr 12, s. 1117-1122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Evidence concerning the importance of angiotensin-converting enzyme (ACE) genotype in cardiovascular diseases is accumulating. The aim of this study was to investigate if nitric oxide (NO), generated from glyceryl trinitrate (GTN), affects human serum ACE activity in vivo, and if so, whether this effect was dependent on ACE genotype and (or) reflected in blood pressure reduction. A tablet containing 5 mg GTN was bucally administered for 5 minutes to 17 healthy volunteers. Blood pressure (BP) was recorded, and serum ACE activity, ACE genotype, and plasma cGMP was analyzed. GTN administration significantly reduced BP only in individuals with the deletion/deletion (DD) genotype. Sixty minutes after GTN administration, serum ACE activity was reduced in individuals with the insertion/insertion (II) and insertion/deletion (ID) genotypes, but not the DD genotype. Comparing the change in ACE activity over time between the genotypes resulted in the following: II vs. DD, p < 0.01, II vs. ID, p < 0.05, and ID vs. DD, p < 0.05. There was no significant difference in plasma cGMp content neither between the ACE genotypes nor before and after GTN administration. In conclusion, GTN inhibits serum ACE in vivo in individuals with the II and ID, but not the DD genotype. © 2005 NRC Canada.

  • 161.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Natural remedies--self care at your own risk! Danger of unknown adverse effects and interactions with "common" medications2005Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102 44, s. 3200-3201Artikkel i tidsskrift (Annet vitenskapelig)
  • 162.
    Powell, Wendy
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Green, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Svensson, Samuel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    A new method for screening the melanin binding ability of different antineoplastic agents.2001Inngår i: Pigment cell research,2001, 2001, s. 397-397Konferansepaper (Fagfellevurdert)
  • 163.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Cherma Yeste, Maria Dolores
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Therapeutic Drug Monitoring of Escitalopram in an outpatient setting2007Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 29, nr 6, s. 758-766Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The main objectives of this study were to outline the inter- and intraindividual and overall pharmacokinetic variability of S-citalopram, S-desmethylcitalopram, and S-didesmethylcitalopram in serum by means of therapeutic drug monitoring, and to investigate potential correlations between the serum concentration and simultaneously collected clinical data. The study was conducted on outpatients in Sweden in 2002 to 2005. Included in the pharmacokinetic evaluation were 155 patients (68% women and 32% men) aged 17 to 95 years (average, 51 years). One serum sample per patient, taken as a trough value in steady state, was assessed. For the inter- and intraindividual variation calculation, 16 patients were included with two eligible samples each. The median daily dose was 20 mg/day (range, 5-40 mg). Extensive overall serum concentration variability was seen for all dose levels. The interindividual coefficient of variation for dose-normalized concentrations was 71% for S-citalopram, 36% for S-desmethylcitalopram, and 50% for S- didesmethylcitalopram. The intraindividual variations over time for the same parameters were approximately 30%, except for the ratio S-desmethylcitalopram/S- citalopram, which was 23%. The median S-desmethylcitalopram level was approximately 60% of the parent substance and the S-didesmethylcitalopram level approximately 9%. Higher age was correlated with higher serum concentrations, but no gender-related concentration differences were found. A majority (76%) of the patients took one or more drugs in addition to escitalopram, but concomitant medication did not seem to interact with escitalopram. However, women taking oral contraceptives showed a lower metabolic ratio compared with age-matched women. As a result of the wide range of the ratio in this population, these findings are not considered of clinical relevance.

  • 164.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Carlsson, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Josefsson, Martin
    Wahldeck, Bertil
    Stereokemi och läkemedelseffekter -ett försummat kunskapsområde2006Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, s. 1305-1311Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

       

  • 165.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-19972003Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 183-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Racemic citalopram (CIT) was introduced in Sweden in 1992 for management of major depression. During a 5-year period, 1992 to 1997, serum samples of CIT and desmethylcitalopram (DCIT) were collected for therapeutic drug monitoring (TDM) from patients from all over Sweden. These samples were accompanied by clinical information on a specially designed TDM request form. They represented men and women of various ages (11-94 years) usually on multiple concomitant medications and treated in a naturalistic setting. The TDM samples eligible for evaluation (n = 749), all trough values at steady state, were studied with respect to inter- and intraindividual pharmacokinetic variability. Extensive, interindividual serum concentration variability was seen on all dose levels. For dose-corrected concentrations (C/D) and for clearance (C1) we found the coefficient of variation (CV) to be approximately 55% for all variables (C/D CIT, C/D DCIT, the ratio DCIT to CIT, and for C1 CIT). The intraindividual variations over time for the same parameters were 30% to 35%. On a population level, signs of a possible saturation of CYP2D6 associated with increasing DCIT-to-CIT ratios with increasing daily doses was observed. Age and gender affected the pharmacokinetics of CIT and DCIT. Women showed significantly higher C/D CIT and C/D DCIT and lower C1 CIT values compared with men, and patients aged more than 65 years had higher C/D CIT and C/D DCIT and lower C1 CIT values compared with younger patients. Finally, concomitant medication affected the outcome of serum concentrations by a general increase in C/D CIT and C/D DCIT but without alteration in the DCIT-to-CIT ratio. Thus, this tendency of changes in the CIT disposition when multiple drugs are used (and multiple diseases are prevailing?) seems more general in character than specific for a certain drug or type of drugs.

  • 166.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Olsson, Gunilla
    Division of Child and Adolescence Psychiatry, Department of Neuroscience, Uppsala University, Uppsala.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Dahl, Marja-Liisa
    Clinical Pharmacology, Department of Medical Sciences, Uppsala University, Uppsala.
    Wålinder, Jan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting2002Inngår i: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 22, nr 4, s. 406-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The prescribing of selective serotonin reuptake inhibitors for adolescents is extensive despite the fact that there are few pharmacokinetic (PK), effi]cacy, safety, or tolerability studies on this group. This study reports the PK findings from two trials in adolescents treated with citalopram (CIT) in naturalistic clinical settings: one retrospective and one prospective. The aim of our study was to describe serum concentrations of CIT, desmethylcitalopram (DCIT), and didesmethylcitalopram (DDCIT) (trough values in steady state) in adolescents in relation to daily dose and clinical information obtained from therapeutic drug monitoring request forms. Altogether, 44 patients younger than 21 years were scrutinized using this combined open-label approach. The main findings were that (1) there was a pronounced interindividual variability of serum CIT, DCIT, and DDCIT concentrations in all doses prescribed, in agreement with previous studies on adults; on correcting for dose, the coefficient of variance was about 50% for CIT, DCIT, and DDCIT; (2) the transformation of CIT to DCIT and of DCIT to DDCIT was similar within the dose range 20 to 60 mg/day; (3) there was a difference between the sexes on comparing the dose-corrected concentrations of CIT and DCIT, with girls presenting significantly higher values than boys; and (4) there was a strong dose-serum concentration relationship in three identified subgroups of adolescents: (a) nonsmokers (CIT, r 2 = 0.71; DCIT, r 2 = 0.81), (b) girls not taking oral contraceptives (CIT, r 2 = 0.75; DCIT, r 2 = 0.71,), and (c) girls in the last 14 days of the menstrual cycle (CIT, r 2 = 0.68; DCIT, r 2 = 0.64). In summary, the present study tentatively supports influences of sex, oral contraceptives, and smoking habits on the disposition of CIT in younger patients. Hence, future studies on CIT should assess these parameters.

  • 167.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Prochazka, Jiri
    Sitsen, Ad
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Inter- and intraindividual pharmacokinetic variations of mirtazapine and its N-demethyl metabolite in patients treated for major depressive disorder: A 6-month therapeutic drug monitoring study2005Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 27, nr 4, s. 469-477Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mirtazapine pharmacokinetic (PK) data from patients on long-term treatment for major depression have never been investigated. For this reason, in a large naturalistic outpatient study (prospective, multicenter, open-labeled, and noncomparative) conducted in Sweden in the period 2000-2002, one of the main objectives was to outline the inter- as well as intraindividual PK variance of mirtazapine and demethylmirtazapine serum concentrations in a patient cohort treated up to 6 (optionally 12) months. A total of 192 male and female outpatients aged 18 years or older were included. Serum samples of mirtazapine and demethylmirtazapine were collected, by the means of therapeutic drug monitoring, at weeks 1, 4, 8, and 24 (52). Altogether 683 serum samples were analyzed. A pronounced interindividual variability of mirtazapine and demethylmirtazapine, and the demethylmirtazapine/mirtazapine ratio was seen. The coefficient of variation was about 38%, 33%, and 36%, respectively. The intraindividual variation over time was low, about 20% on all variables. At the population level, no accumulation of mirtazapine, demethylmirtazapine, or change of the demethylmirtazapine/mirtazapine ratio was observed over time. Women had significantly higher dose-corrected concentrations of mirtazapine and demethylmirtazapine and demethylmirtazapine/mirtazapine ratio than men. Patients above 65 years of age had higher concentrations than their younger counterparts. Among patients with adverse events, lower demethylmirtazapine concentrations were observed than in patients with no adverse events. Patients on multiple drug treatment had higher dose-corrected mirtazapine and demethylmirtazapine serum concentrations than patients taking only mirtazapine. Weight and BMI had a significant negative correlation with demethylmirtazapine concentrations and with the demethylmirtazapine/mirtazapine ratio. Continued efforts are warranted to perform PK studies in a natural clinical setting to learn and understand inter- and intraindividual PK variances in real patients treated for longer periods of time. For mirtazapine as well as for most antidepressant drugs only relatively short term PK is available. To help clinicians improve their treatment of patients with major depressive disorder, the possible implications on the PK with a long-term treatment are important to study. Copyright © 2005 by Lippincott Williams & Wilkins.

  • 168.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Åberg-Wistedt, Anna
    Institute of Clinical Neuroscience, Department of Psychiatry, Karolinska Institute, Stockholm, Sweden.
    Ågren, Hans
    Karolinska Institute, Neurotec, Department Division of Psychiatry, Huddinge University Hospital, Huddinge, Sweden.
    Höglund, Peter
    Institute of Laboratory Medicine, Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund, Sweden.
    Åkerblad, Ann-Charlotte
    Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
    Bengtsson, Finn
    Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
    Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression2004Inngår i: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 19, nr 5, s. 283-291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50–150 mg daily) and paroxetine (20–60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient.

    1 A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for desmethylsertraline, 27% for the ratio desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day). The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%, indicating intraindividual metabolizing stability over time. Both sertraline and paroxetine displayed sex differences in the dose-concentration correlation.

    2 It was possible to predict sertraline, but not paroxetine, steady state levels.

    3 The terminal elimination t½ for both drugs after 6 months of treatments was similar to data previously reported from short-term withdrawal studies.

    4 No correlation between serum drug concentrations and clinical effect was detected for either sertraline or paroxetine.

    For the future, continuous efforts are warranted to perform PK investigations in the natural clinical setting in which the drugs are usually prescribed.

  • 169.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Åberg-Wistedt, Anna
    Karolinska Institute, Department of Psychiatry, Stockholm, Sweden.
    Ågren, Hans
    Karolinska Institute, Neurote Department, Division of Psychiatry, Huddinge, Sweden.
    Åkerblad, Ann-Charlotte
    Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations2004Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, nr 3, s. 443-446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A recent estimation in a psychiatric cohort showed numbers of noncompliance between 10% and 60%. Therapeutic drug monitoring (TDM) is one method assessing compliance by analysis of drug concentration in the blood.

    Method: During a 24-week phase IV clinical trial, five repeated serum samples of sertraline (SERT) and N-desmethylsertraline (DSERT), trough values in steady state, were collected per patient. Previous results show that the intraindividual variation over time of the ratio DSERT/SERT is low. Hence, we hypothesized that significant partial noncompliance could be scrutinized further by an assessment of the DSERT/SERT ratio. The main aim was to test the applicability of a novel type of TDM procedure based on repeated metabolite/parent compound ratio measurements.

    Result: 9.4% of the per-protocol population in the trial (n=96) were in either hidden total (n=4) or hidden partial (n=5) noncompliance. Only by using the novel TDM ratio screening method could a majority of these patients be identified.

  • 170.
    Rosenqvist, U
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Törnqvist, M
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Therapeutic Drug Monitoring: An interaction between sertraline ana Carbamazepine which resulted in sub-therapeutic concentrations of sertraline and N-desmethyl.2003Inngår i: Skriv in din egen text för ej reg. tidskrift etc.,2003, 2003, s. 527-527Konferansepaper (Fagfellevurdert)
  • 171. Samuelsson, E
    et al.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Incidence of venous thromboembolism in young Swedish women and possibly preventable cases among combined oral contraceptive users2004Inngår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 83, nr 7, s. 674-681Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. We wanted to study the incidence of venous thromboembolism (VTE), acquired risk factors of VTE and preventable cases among users of combined oral contraceptives (COCs). Methods. All women aged 15-44 years, (n = 24 373) living in the county of Jämtland, Sweden, between 1991 and 2000, constituted the study base in a retrospective case-reference study. Women with VTE were identified through hospital registers and interviewed by telephone. The utilization of COCs according to age was obtained from a prospective prescription database, and data from national health databases were used. Results. Of 88 women with first-time VTE, 43 (49%) were COC users and 13 (15%) were pregnant. All women had at least one known risk factor, and 51 (58%) women had combinations of risk factors. The total incidence rate of VTE per 100000 women-years for all women were 36 (29-44), for nonusers 19 (12-25) for women using third generation COCs 115 (67-184), for women using other COCs 60 (37-83), and for women during pregnancy and postpartum 103 (55-177). Of the total 244000 women-years represented, COC users constituted 24%, pregnant women 5%, and women with other acquired risk factors 5%. The corresponding incidence rates after excluding VTE cases with other acquired risk factors were 10 (6-14), 1.2 (0.14-44), 64 (29-121), 27 (13-48), and 59 (24-121), per 100000 women-years. In 11 (26%) of the COC-related VTE cases, there were relative contraindications for use of COCs or lack of thromboprophylaxis in relation to surgery. Conclusion. We found a very low incidence of idiopathic VTE among young non-OC users. The incidence of VTE during pregnancy was only slightly higher than during COC use. It was considered that a significant part of COC-related VTE might have been avoided.

  • 172.
    Schmekel, Birgitta
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Hjärtcentrum, Fysiologiska kliniken.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Malmström, M
    Venge, P
    Eosinophil cationic protein (ECP) in saliva: A new marker of disease activity in bronchial asthma2001Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 95, nr 8, s. 670-675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Eosinophil cells play a crucial role in the pathogenesis of asthma, and concentration of eosinophil cationic protein (ECP) in serum has been used to monitor activity of the disease. Our aim was to determine the feasibility and usefulness of measuring ECP in saliva and to use it as a marker of the disease. Thirty-eight patients with asthma and 16 healthy volunteers were included in this study. Repeatability of measurements of ECP in saliva was acceptable [intra-class correlation coefficients (Ri) = 0.74 and coefficients of repeatability (CR) = 0.37 in five healthy subjects]. Levels of ECP in saliva were higher in asthmatics than in volunteers (P < 0.01). There was a significant inverse association between a surrogate variable reflecting disease activity (i.e. change over a few weeks in dose of inhaled corticosteroid required by a change in clinical status of asthma) and a change over the same time period in salivary ECP in 19 patients with stable asthma (r = -0.64, P = 0.02). Our findings indicate that levels of salivary ECP are elevated in patients with asthma and associated with presumed activity of disease as recorded by alteration of taken dose of inhaled corticosteroid. ⌐ 2001 Harcourt Publishers Ltd.

  • 173.
    Schmekel, Birgitta
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Linköpings universitet, Hälsouniversitetet.
    Rydberg, Irene
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Naidu Sjöswärd, Kerstin
    Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Andersson, Rolf
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers1999Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 13, nr 6, s. 1230-1235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Racemic R,S-salbutamol is taken to relieve bronchial constriction. Only the R-enantiomer has bronchodilating properties. The S-enantiomer has been proposed to cause in vitro bronchial hyperreactivity in guinea-pigs. Stereoselective elimination of salbutamol has been shown, with S-salbutamol being eliminated at a slower rate than R-salbutamol. This study questioned whether rates of stereoselective elimination were similar after oral or lung delivery, and whether the S:R ratio would increase after repeated inhalations in a situation resembling a common clinical use. Eighteen healthy volunteers received single-dose racemic salbutamol as a solution instilled in the trachea during anaesthesia, as inhaled micronized powder and/or as ingested tablets. Five volunteers inhaled repeated doses of racemic salbutamol. Concentrations in plasma and urine were measured using a technique which allowed chiral separation of samples with concentrations as low as 0.1 ng·mL -1. The bioavailability of S-salbutamol was significantly higher than that of R-salbutamol after the different modes of administration. Stereoselective elimination was more pronounced after oral administration than after inhalation. Repeated inhalations resulted in successive increases in the S:R ratio as steady state was approached. In conclusion, the clinical consequences of increasing plasma concentrations of S-salbutamol need to be further assessed.

  • 174.
    Sjöwall, Christoffer
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Reumatologi.
    Bengtsson, Torbjörn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Skogh, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    CRP and anti-CRP autoantibodies in systemic lupus erythematosus.2005Inngår i: Current rheumatology reviews, ISSN 1573-3971, Vol. 1, s. 81-89Artikkel i tidsskrift (Fagfellevurdert)
  • 175. Spigset, O
    et al.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Nya antidepressiva under graviditet och amning2004Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101 13, s. 1176-1181Artikkel i tidsskrift (Annet vitenskapelig)
  • 176.
    Spigset, Olav
    et al.
    Trondheim.
    Bate, Andrew
    Uppsala.
    Ståhl, Malin
    Uppsala.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Venous thromboembolism during treatment with antipsychotics2006Inngår i: 22nd International Conference on Pharmacoepidemiology Therapeutic Risk Management,2006, 2006, s. S223-S223Konferansepaper (Annet vitenskapelig)
    Abstract [en]

      

  • 177.
    Svensson, Samuel
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Melanophore a2-Adrenoceptors.1993Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The present study provides new insight into the pharmacology, the signal transduction mechanisms and the molecular biology of a2-adrenoceptors (a2-ARs) in black pigment cells (melanophores) of a teleost fish, the cuckoo wrasse (Labrus ossifagus L.). Stimulation of these receptors leads to an aggregation of intracellular pigment granules, which is the cellular mechanism underlying the ability of fishes to change color.

    The pharmacology of the melanophore a2-AR is very similar to its mammalian counterparts. However, the melanophore a2-AR is unique in one respect, UK 14,304, a potent agonist at mammalian a2-ARs, is an antagonist in melanophores.

    Noradrenaline and the selective a2-AR agonist B-HT 920 are pharmacologically heterogeneous regarding their ability to induce pigment aggregation. This may reflect that B-HT 920 and noradrenaline interact with different a2-AR sites.

    Pigment aggregation induced by a2-ARs seems to involve multiplesignaling pathways. Attenuation of intracellular cAMP production and a subsequent reduction of protein kinase A activity may serve as one mechanism, and an additional signal mechanism may involve activation of a phosphatase.

    An a2-adrenoceptor (a2p) from L. ossifagus skin mRNA was cloned. The deduced amino acid sequence showed significant homology with the human a2-ARs. When expressed in a mammalian cell line, the pharmacology of the <X2F was found to be very similar that of the in situ melanophore a2-ARs. The <X2F showed characteristics of both the human a2CIO and a2C4, indicating that <X2F may represent traces of an ancestral subtype.

    Melanin-concentrating hormone (MCH) induces pigment aggregationthrough a unique receptor. However, MCH receptors and a2-ARs might share a common signal transduction mechanism, namely attenuation of cAMP production.

    When melanophores are maintained in tissue culture media, the sensitivity to noradrenaline is increased and the sensitivity to MCH is decreased. This reciprocal change in sensitivity may be due to an increase in a2-AR coupling at the expense of MCH receptor couplingand/or to a down regulation of MCH receptors.

  • 178.
    Svensson, Samuel
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
    Lindgren, Sofi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Powell, Wendy
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Green, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells2003Inngår i: Pigment Cell Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 16, nr 4, s. 351-354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study we have developed a simple method to elucidate the melanin binding ability of different chemotherapeutic agents. The anthracyclines, doxorubicin and daunorubicin, or the alkylating agent cisplatin were preincubated with melanin (Sepia). Melanin and free drug was then separated through centrifugation and the cytotoxic effects of corresponding drug were evaluated in a MTT (3-(4,5-dimetyltiazol-2-yl)-2,5-difenyl-tetrazoliumbromide) assay using MOLT-4 cells. Our results show that melanin pretreatment shifted the IC50 value for doxorubicin from 0.06 to 0.97 ╡M and for daunorubicin from 0.04 to 0.80 pM. In contrast, the IC50 values of cisplatin was not influenced by melanin pretreatment indicating that cisplatin does not bind to melanin. By comparing equi-active concentrations from concentration-response curves with or without melanin pretreatment an approximate binding capacity of melanin could be estimated. Our results show that melanin binds about 900 nmol/mg doxorubicin and 760 nmol/mg daunorubicin. Chloroquine, which is known to bind to melanin with high affinity, was found to inhibit melanin binding of both daunorubicin and doxorubicin, thereby leading to an increased sensitivity of the anthracyclines. The clinical implications of melanin binding regarding unwanted accumulation of anthracyclines in the skin as well as chemoprotective effects against chemotherapy are discussed.

  • 179. Tishelman, Carol
    et al.
    Backman, Lise-Lott
    Bernhardsson, Britt-Marie
    Johansson, Eva
    Börjeson, Sussanne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Blomberg, Karin
    What is needed to improve quality of care for patients with advanced cancer? Results of focus group discussions with staff.2001Inngår i: Eur J Cancer,2001, 2001, s. 383-383Konferansepaper (Fagfellevurdert)
  • 180.
    Tishelman, Carol
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Bernhardsson, Britt-Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Backman, Lise-Lotte
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Ternestedt, Britt-Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Börjeson, Sussanne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Blomberg, Karin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Johansson, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Levealahti, Helena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Imporving quality of care for patients with advanced cancer through a knowledge exchange program.2001Inngår i: Eur J Cancer,2001, 2001, s. 409-409Konferansepaper (Fagfellevurdert)
  • 181.
    Tjäderborn, Micaela
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi. National Board of Forensic Medicine, Linköping, Sweden.
    Jönsson, Anna
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi. National Board of Forensic Medicine, Linköping, Sweden.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Fatal unintentional intoxications with tramadol during 1995-20052007Inngår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 173, nr 2-3, s. 107-111Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 μg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 μg/g (range 1.1-12.0 μg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients. © 2007 Elsevier Ireland Ltd. All rights reserved.

  • 182.
    Torfgård, Kristina E.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Glyceryl Trinitrate Distribution and the "Remarkable Tolerance"1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    To study the distribution of glyceryl trinitrate (GTN), a gas chromatographic method was developed for simultaneous determination of GTN and its dinitrate metabolites in 'plasma and tissues. The distribution of GTN and 1 ,3-g1yceryl dinitrate (1,3-GDN) and 1,2-glyceryl dinitrate (1,2-GDN) was studied in GTN tolerant and nonto1erant rats. An extensive distribution of GTN and GDNs was found, and the highest level of GTN was observed in the adipose tissue of both tolerant aud nontolerant animals. This subcutaneous depot of GTN might affect the pharmacokinetics of the drug. Generally higher concentrations of GTN were found in tissues studied (except for the liver), as compared with blood. Furthermore, high levels of GTN and GDNs were found in the brain, and an increase in cGMP level was also observed there, which might mediate side effects, such as headache, head throbbing and dizziness. The formation of the metabolites 1,3-GDN and 1,2-GDN in plasma werefound to be dependent on the GTN concentration.

    Long-term administration of GTN was shown to result not only in tolerance, i.e. reduced response to a given dose on repeated administration, but in a decreased elimination rate of GTN, 1,3-GDN, and 1,2-GDN in plasma. Moreover, GTN tolerance was found to reduce both the maximal relaxation and the potency of GTN. An increase in cGMP was found in tolerant vessels, although this was more marked in nontolerant vessels. The cGMP levels noted in vessels do not correlate with tissue GTN levels in rats.

    Autoradiographic studies show a rapid and homogeneous distribution of radioactivity after iv [14C]-GTN in mice aud rat. Cytochrome P-450 and esterases were found to be involved in the distribution of radioactivity.

    The present thesis shows that the phosphodiesterase inhibitor dipyridamole can not reverse GTN tolerance in healthy volunteers. Based on this and on previous studies on GTN tolerance, it was concluded that GTN tolerance in humans can only be reversed by applying "nitrate free intervals".

  • 183. Wester, Karin
    et al.
    Jönsson, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Fatala läkemedelsbiverkningar - spontanrapporterade fall i Sverige 1995 - 20042005Inngår i: Läkarsällskapets Riksstämma,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 184.
    Wester, Karin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa.
    Jönsson, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spigset, Olav
    Olso, Norge.
    Druid, Henrik
    Stockholm.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Incidens av läkemedelsrelaterad dödslighet i Sverige2007Inngår i: Läkarsällskapets Riksstämma,2007, 2007Konferansepaper (Annet vitenskapelig)
  • 185.
    Wester, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och vård.
    Jönsson, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spigset, Olav
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spontaneously reported fatal adverse drug reactions: a 10-year survey from Sweden2006Inngår i: International conference on Pharmacoepdemiology Therapeutic risk management,2006, 2006Konferansepaper (Annet vitenskapelig)
  • 186.
    Wester, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Anna
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spigset, Olav
    St. Olav University Hospital, Trondheim, Norway.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spontaneously reported fatal suspected adverse drug reactions: A 10-year survey from Sweden2007Inngår i: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 16, nr 2, s. 173-180Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: One of the main methods for monitoring the safety of marketed drugs is spontaneously reporting of suspected adverse drug reactions (ADRs). The objective of this study was to describe the pattern of spontaneously reported fatal adverse drug reactions (FADRs) by analysing data from the national spontaneous reporting system in Sweden. Methods: In Sweden it is compulsory to report all new or serious suspected ADRs to the Medical Products Agency. The information in these reports is stored in the national database SWEDIS (Swedish Drug Information System). All suspected FADRs reported to SWEDIS between 1 January 1995 and 31 December 2004 were reviewed and analysed. Results: During the study period 990 reports of FADRs were found. The main distribution of suspected FADRs was: haemorrhages (n = 603, 60.9%), blood and bone marrow dysfunction (n = 71, 7.2%), sudden death (n = 38, 3.8%) and pulmonary embolism (n = 30, 3.0%). Antithrombotic agents were the drugs most frequently implicated in the FADRS (n = 605, 61.1%). Vitamin K antagonists were reported in 453 cases (45.8%) and acetylsalicylic acid in 82 cases (8.3%). Among the fatalities with blood and bone marrow dysfunction methotrexate was the most frequently reported drug. For sudden death and pulmonary embolism, antipsychotics and oestrogen containing drugs, respectively, were most commonly reported. Conclusions: Bleeding complications amounted more than half of all reports of FADRS and vitamin K antagonists were implicated in most of these reports. However, as spontaneous reporting systems are primarily set up for signalling purposes, the data must be interpreted with utmost care. Copyright © 2006 John Wiley & Sons, Ltd.

  • 187. Wikell, C
    et al.
    Apelqvist, G
    Carlsson, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hjorth, S
    Bergqvist, P B F
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Pharmacokinetic and pharmacodynamic responses to chronic admininstration of the selective serotonin reuptake inhibitor citalopram in rats.2000Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 22, s. 327-336Artikkel i tidsskrift (Fagfellevurdert)
  • 188. Wikell, C
    et al.
    Eap, CB
    Josefsson, M
    Apelqvist, G
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Baumann, P
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment2002Inngår i: Chirality, ISSN 0899-0042, E-ISSN 1520-636X, Vol. 14, nr 4, s. 347-350Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS, 97 and 66 nM in normal rats, median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS, 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = 1.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy. ⌐ 2002 Wiley-Liss, Inc.

  • 189. Wikell, Cecilia
    et al.
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Hjorth, Stephan
    Apelqvist, Gustav
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Effect of halving the dose of venlafaxine to adjust for putative pharmacokinetic and pharmacodynamic changes in an animal model of chronic hepatic encephalopathy2001Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 24, nr 6, s. 324-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with chronic hepatic encephalopathy display monoaminergic perturbations together with affective symptoms. Thus, these patients belong to a group with a probability of receiving antidepressant drug treatment. The liver impairment may result in pharmacokinetic alterations of the antidepressant drug, which in turn may affect the already perturbed monoaminergic function. Venlafaxine (VEN) was administered as a single subcutaneous challenge to portacaval shunted (experimental hepatic encephalopathy model) rats (5 mg/kg) and sham-operated rats (5 and 10 mg/kg). The aims were to investigate whether a reduced dose in portacaval shunted rats resulted in higher concentrations of VEN and serotonin as compared to control rats, which had been demonstrated earlier when the rats received the same dose (10 mg/kg). A 50% reduction of the dose of VEN administered to portacaval shunted rats resulted in elevated levels of VEN in serum, brain parenchyma, and brain dialysate about 300 minutes after the injection. The VEN challenge increased the serotonin and noradrenaline concentrations in dialysate in portacaval shunted rats and both sham groups, but the three VEN groups did not differ in any major way in serotonin and noradrenaline output. Therefore, when the dose of VEN administered to experimental hepatic encephalopathy was reduced 50% as compared to control rats, mainly pharmacokinetic, and possibly also monoaminergic, alterations were observed.

  • 190.
    Wålinder, Jan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Prochazka, J
    Odén, A
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Dahl, ML
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Mirtazapine naturalistic depression study (in Sweden) - MINDS(S): Clinical efficacy and safety2006Inngår i: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 21, nr 3, s. 151-158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety. Method: An open-labelled, prospective, multicenter, non-comparative trial was conducted during a 2-year period in patients with major depression according to DSM-IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events. Results: 192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall. Conclusion: The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population. Copyright © 2006 John Wiley & Sons, Ltd.

  • 191.
    Wårdell, Karin
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Hoffman, Mikael
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Ilias, Michail
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Salerud, Göran
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik.
    Stücker, M.
    Karaktärisering av blodperfusionen I hudlesioner med laser Doppler perfusion imaging2000Inngår i: Svenska Läkarsällskapets Riksstämma,2000, 2000, s. 249-249Konferansepaper (Annet vitenskapelig)
  • 192. Åkerblad, AC
    et al.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Ekselius, L
    von Knorring, L
    Effects of an educational compliance enhancement programme and therapeutic drug monitoring on treatment adherence in depressed patients managed by general practitioners2003Inngår i: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 18, nr 6, s. 347-354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Medication non-adherence is a major obstacle in the treatment of affective disorders. The primary objective of this study was to evaluate two different interventions to improve adherence to antidepressant drugs. Secondary objectives included response to treatment, relation between adherence and response, patient satisfaction and tolerability. A randomized controlled design was used to assess the effect of a patient educational compliance enhancing programme (CP) and therapeutic drug monitoring in 1031 major depressed patients treated with sertraline for 24 weeks and managed by their general practitioner. Adherence was measured by questioning, measurable serum levels of sertraline and desmethylsertraline, appointments kept and a composite index including all three methods. Treatment adherence was found in 37-70% of patients, depending on the method used. Neither of the interventions resulted in a significant increase in adherence rate. However, significantly more patients in the CP group had responded at week 24 compared to patients in the control group. Overall, significantly more adherent patients responded to treatment compared to non-adherent patients, regardless of method used to determine adherence. This large study demonstrates that treatment response increases when using an educational compliance programme and that a strong relationship between treatment adherence and response exists. ⌐ 2003 Lippincott Williams & Wilkins.

  • 193. Åkerblad, AC
    et al.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    von Knorring, L
    Ekselius, L
    Response, remission and relapse in relation to adherence in primary care treatment of depression: A 2-year outcome study2006Inngår i: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 21, nr 2, s. 117-124Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Non-adherence to antidepressant drug treatment is common. In a recent study in depressed primary care patients, we reported a strong relationship between adherence and response after 6 months. With the use of a naturalistic design, the patients in that study were prospectively followed for 2 years. The purpose of the present study was to investigate the patients' long-term outcome and, in particular, to examine the impact of patients' treatment adherence on response, remission and relapse. Of the 1031 patients in the intent-to-treat (ITT) sample, 835 completed the study. After 2 years, the overall remission rate defined as a Montgomery-Åsberg Depression Rating Scale score of nine or less was 68% in the ITT sample analysed with the last observation carried forward (LOCF) technique, and 75% in observed cases. In total, 34% of the responders experienced at least one relapse. Response rates (LOCF) were significantly higher in adherent compared to non-adherent patients at week 24 [95% confidence interval (CI) = 21.4-32.1], year 1 (95% CI = 12.3-22.2) and year 2 (95% CI = 9.2-19.0). Remission rates (LOCF) were also significantly higher in the group of adherent patients at week 24 (95% CI = 9.6-21.5), year 1 (95% CI = 10.0-21.5) and year 2 (95% CI = 11.0-22.0). No relationship between adherence and relapse rate was observed, although the mean time from response to first sign of relapse was significantly longer in the adherent patients (95% CI = 9-97 days). In conclusion, this 2-year follow-up study showed superior long-term recovery in patients who were adherent to antidepressant medication compared to non-adherent patients. © 2006 Lippincott Williams & Wilkins.

  • 194.
    Öhman, Daniel
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bioanalytical development for application in therapeutic drug monitoring: focus on drugs used in psychiatry2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Introduction: Since the 1950s and onwards, many new psychoactive drugs have been successfully introduced in clinical practice. A common feature of these drugs is a profound metabolism before clearance from the body. Genetic and phenotypic factors among patients can be anticipated to interact with the metabolism and therefore a major variance in the drug concentration between patients upon the same dose may be found. In later years there has been an increasing awareness, that the individual drug metabolism and drug body disposition do not only refer to the parent compound and major metabolites but also to the separate enantiomers in the case of chiral drugs.

    Bioanalytical methods for determination of drug concentrations have constantly been developed to assess the large pharmacokinetic variability of these drugs. Moreover, in the psychopharmacological practice these methods are often extended into a "Therapeutic Drug Monitoring (TDM) Service". A TDM service is used to determine the patient-specific drug analytical outcome in order to assess the precision in dose prescription as well as to recommend adequate dose adjustments for a particular patient.

    Aim: The aim was to develop bioanalytical methods, utilising high performance liquid chromatography, for serum determinations in patients under chronic dosing schedules for some recently introduced drugs used in psychiatry.

    Firstly, for the antidepressant drug reboxetine by an achiral methodology (paper I) consecutively extended to an enantioselective methodology for the individual enantiomers of the drug (paper II and III). Thereafter, after the evaluation of on-line extraction as an automated alternative to manually performed solid phase extraction for sample preparation (paper IV), apply on-line extraction in combination with ion-trap mass spectrometry detection for serum determination of the novel antipsychotic drug ziprasidone (paper V).

    Results and Conclusion: The methodology described in paper I has been applied on more than 500 patient samples from the naturalistic clinical practice as well as from controlled clinical trials. The methodology has proven robust and reliable and, although manually performed, easy to handle. The kinetic outcome display a great variability in concentration outcome even within the same prescribed dose, i.e. through level samples in steady-state were found to be 660±400 nM on 8 mg/day.

    Paper II, which describes the development of three approaches for direct chiral separation of reboxetine and O-deethylreboxetine enantiomers in the reversed phase mode, is in itself new and important. It is however, after applying MS2 detection, in paper III that the methodology is extended to include patients, i.e. patients from two separate clinical trials. Trial I comprised 23 patients on monotherapy with reboxetine and trial II comprised 47 patient from a naturalistic clinical setting. The pharrnacokinetic outcome displayed a S,S- over R,R-reboxetine ratio of about 0.5 with a rather pronounced inter-individual ratio (i.e. 0.2 to 0.9). The enantiomeric ratio did not correlate to the overall reboxetine concentration and the enantiomeric ratio was about 30% higher in females than in males. Repeated samples were analysed for trial I patients displaying an inter-individual coefficient of variation (CV) of about 17% meanwhile the intra-individual CV was about 4%. Calculating the noradrenaline reuptake inhibition (NARI) -activity out of the individual enantiomeric ratios showed that females may have a higher NARI-activity than males at a given reboxetine concentration.

    Paper IV proves that online extraction offers a robust, reliable and, for the analyst, time saving alternative (above 80%) to manually performed off-line solid phase extraction for sample preparation (citalopram and its demethylated metabolites were used as model substances).

    Paper V describes the development of a TDM process for ziprasidone and its S-methylated metabolite. The sample handling as well as the analytical process was subjected to a solid and satisfactory validation. It was proved that the lack of selectivity during on-line extraction can be compensated for by a selective form of detection, i.e. mass spectrometric detection.

    Delarbeid
    1. Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC
    Åpne denne publikasjonen i ny fane eller vindu >>Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC
    2001 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 23, nr 1, s. 27-34Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Reboxetine isa new antidepressant drug acting as a potent and selective noradrenaline reuptake inhibitor on the noradrenergic neuronal system. Because of an expected interindividual variability in drug metabolism in the clinical practice the need for therapeutic drug monitoring routines in psychiatry is always a prominent feature. In this application, the preferred bioanalytic methodology was solid phase extraction combined with reversed-Phase high-Performance liquid chromatography and ultraviolet detection at 210 nm. The technique proved reliable, with interday and intraday variation of less than 5% and a quantification limit for reboxetine and one of its main metabolites O-Desethylreboxetine (O-Reboxetine) at 5 and 30 nmol/L, respectively. The method was applied on serum samples from 38 patients treated chronically with reboxetine. These samples were drawn as trough levels in steady state with a dosage range of 2-16 mg/day. They evidenced a mean reboxetine concentration that was fairly linear and dose proportional, although the variance in concentration was large between patients, even those taking the same dosage. O-Reboxetine was detected in quantifiable amounts in only 1 of the 38 patients (<3%). In conclusion, these results suggest that a routine reboxetine therapeutic drug monitoring service that is robust enough to produce reliable and reproducible results may be introduced into everyday clinical practice.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27057 (URN)10.1097/00007691-200102000-00006 (DOI)11206039 (PubMedID)11703 (Lokal ID)11703 (Arkivnummer)11703 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Simultaneous determination of reboxetine and O-desethylreboxetine enantiomers using enantioselective reversed-phase high-performance liquid chromatography
    Åpne denne publikasjonen i ny fane eller vindu >>Simultaneous determination of reboxetine and O-desethylreboxetine enantiomers using enantioselective reversed-phase high-performance liquid chromatography
    2002 (engelsk)Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 947, nr 2, s. 247-254Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Current knowledge of stereoselective pharmacokinetics and different potencies of drug enantiomers requires the performance of stereoselective analysis during therapeutic drug monitoring in clinical practice. However, in the case of the new antidepressant drug reboxetine, no effort has been made so far to find a such a suitable system. Therefore, as a step towards developing an enantioselective bioanalytical method for reboxetine and the O-desethylreboxetine metabolite, three stereoselective chromatographic approaches have been investigated. Several chiral columns were tested, among them Chiral-AGP, ChiraGrom 2 and Chiral-CBH, which were able to simultaneously separate the two compounds into enantiomers in total running times of 28, 18 and 12 min, respectively.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27058 (URN)10.1016/S0021-9673(02)00012-2 (DOI)11704 (Lokal ID)11704 (Arkivnummer)11704 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Determination of serum reboxetine enantiomers in patients on chronic medication with racemic reboxetine
    Åpne denne publikasjonen i ny fane eller vindu >>Determination of serum reboxetine enantiomers in patients on chronic medication with racemic reboxetine
    2003 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 174-182Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The chiral compound reboxetine is used as a selective noradrenaline re-uptake inhibitor (NARI) for the treatment of major depressive disorders. The pharmacokinetic variability of the enantiomers of the drug (S,S- and R,R-reboxetine) was studied using stereoselective high-performance liquid chromatography with mass spectrometric detection in a controlled clinical monotherapy situation (trial I) and a naturalistic clinical setting (trial II). Trial I included patients receiving racemic reboxetine as 6-month monotherapy for treatment of major depressive disorder. Trough level serum samples in steady state were analyzed for the concentration of the reboxetine enantiomers in study weeks 4, 12, and 24. In a therapeutic drug monitoring setting (trial II), 47 patients on doses ranging from 4 to 16 mg daily, including much polypharmacy, trough level steady-state serum samples were analyzed by the same bioanalytical method. Data from trials I and II were assessed to determine the inter- and intraindividual pharmacokinetic outcomes. The results showed that the median S,S/R,R ratio in steady state was 0.5 and ranged from 0.22 to 0.88. It was also shown that women have an approximately 30% higher S,S/R,R ratio than men. The S,S/R,R ratios of reboxetine were not found to correlate with reboxetine concentrations. To investigate the NARI activity of a circulating serum reboxetine concentration, a recalculation of the determined enantiomeric concentrations to previously demonstrated experimental NARI potencies of the drug enantiomers was performed. This partly novel concept of estimating pharmacodynamic activity showed that the serum NARI activity in women tended to be higher than in men at a given reboxetine concentration. In conclusion, the variability in the NARI activity per nmol/L reboxetine and the variability in the concentration outcome of the reboxetine enantiomers may justify the use of enantioselective drug monitoring in the clinic. The gender aspects of the drug have to be further assessed.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26798 (URN)10.1097/00007691-200304000-00006 (DOI)11406 (Lokal ID)11406 (Arkivnummer)11406 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. On-line extraction using an alkyl-diol silica precolumn for racemic citalopram and its metabolites in plasma: results compared with solid-phase extraction methodology
    Åpne denne publikasjonen i ny fane eller vindu >>On-line extraction using an alkyl-diol silica precolumn for racemic citalopram and its metabolites in plasma: results compared with solid-phase extraction methodology
    2001 (engelsk)Inngår i: Journal of Chromatography B: Biomedical Sciences and Applications, ISSN 1387-2273, E-ISSN 1878-5603, Vol. 753, nr 2, s. 365-373Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Sample preparation is usually the most critical and time consuming step when using HPLC for drug analysis in biological matrixes. Sample extracts have to be clean considering both chromatographic interferences and column maintenance. To meet some of these criteria a fully automated on-line extraction (OLE) analysis method was developed for the antidepressant drug citalopram and its two demethylated metabolites, using an RP-C4-ADS extraction column. A comparison between the new OLE method and an off-line solid-phase extraction method showed that the two methodologies were equal in analytical precision but that the OLE method was faster and therefore superior in sample capacity per day.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26834 (URN)10.1016/S0378-4347(00)00579-X (DOI)11449 (Lokal ID)11449 (Arkivnummer)11449 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Biolanalysis of ziprasidone and its S-methylated metabolite in serum using on-line extraction and liquid chromatography-masspectrometry
    Åpne denne publikasjonen i ny fane eller vindu >>Biolanalysis of ziprasidone and its S-methylated metabolite in serum using on-line extraction and liquid chromatography-masspectrometry
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The novel antipsychotic agent Ziprasidone, (Zip) was introduced for clinical prescription in Sweden in the early spring of 2001. As of yet, no bioanalytical procedure suitable for a Therapeutic Drug Monitoring (TDM)-service of the drug has been presented. Therefore a bioanalytical methodology utilising online extraction on RP-C4-ADS columns combined with ion-trap masspectrometric detection for determination of Zip and its S-methylated metabolite (Smd-Zip) was developed. The stability of the analytes in serum was determined for establishing a correct sample handling procedure.

    The calibration model for Zip and Smd-Zip had a linear response function in the concentration range 20 to 500 and 15 to 300 nM, respectively. The intra- and inter-day coefficient of variance was below 10% for all calibrator levels for both Zip and Smd-Zip. Validation of the sample handling procedure showed that samples are stable in room temperature or refrigerator for 3 days. Repeated freeze/thaw cycles, for five times did not affect the Zip or Smd-Zip concentration. In essence these findings state the importance of a correct sampling procedure for a functional ID M-procedure.

    The TDM-procedure was applied on 10 patient serum samples obtained from a naturalistic clinical setting. The obtained concentrations, ranging from 66 to 432 nM for Zip and 42 to 220 nM for Smd-Zip were within the dynamic range of the present methodology. Thus, a future utility for this newly developed method in a TDM-setting seems evident.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84595 (URN)
    Tilgjengelig fra: 2012-10-15 Laget: 2012-10-15 Sist oppdatert: 2012-10-15bibliografisk kontrollert
  • 195.
    Öhman, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Björkman, Helena
    Department of Analytical Chemistry, Stockholm University, Stockholm, Sweden.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Biolanalysis of ziprasidone and its S-methylated metabolite in serum using on-line extraction and liquid chromatography-masspectrometryManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The novel antipsychotic agent Ziprasidone, (Zip) was introduced for clinical prescription in Sweden in the early spring of 2001. As of yet, no bioanalytical procedure suitable for a Therapeutic Drug Monitoring (TDM)-service of the drug has been presented. Therefore a bioanalytical methodology utilising online extraction on RP-C4-ADS columns combined with ion-trap masspectrometric detection for determination of Zip and its S-methylated metabolite (Smd-Zip) was developed. The stability of the analytes in serum was determined for establishing a correct sample handling procedure.

    The calibration model for Zip and Smd-Zip had a linear response function in the concentration range 20 to 500 and 15 to 300 nM, respectively. The intra- and inter-day coefficient of variance was below 10% for all calibrator levels for both Zip and Smd-Zip. Validation of the sample handling procedure showed that samples are stable in room temperature or refrigerator for 3 days. Repeated freeze/thaw cycles, for five times did not affect the Zip or Smd-Zip concentration. In essence these findings state the importance of a correct sampling procedure for a functional ID M-procedure.

    The TDM-procedure was applied on 10 patient serum samples obtained from a naturalistic clinical setting. The obtained concentrations, ranging from 66 to 432 nM for Zip and 42 to 220 nM for Smd-Zip were within the dynamic range of the present methodology. Thus, a future utility for this newly developed method in a TDM-setting seems evident.

  • 196.
    Öhman, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Cherma Yeste, Maria Dolores
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Determination of serum reboxetine enantiomers in patients on chronic medication with racemic reboxetine2003Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 174-182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The chiral compound reboxetine is used as a selective noradrenaline re-uptake inhibitor (NARI) for the treatment of major depressive disorders. The pharmacokinetic variability of the enantiomers of the drug (S,S- and R,R-reboxetine) was studied using stereoselective high-performance liquid chromatography with mass spectrometric detection in a controlled clinical monotherapy situation (trial I) and a naturalistic clinical setting (trial II). Trial I included patients receiving racemic reboxetine as 6-month monotherapy for treatment of major depressive disorder. Trough level serum samples in steady state were analyzed for the concentration of the reboxetine enantiomers in study weeks 4, 12, and 24. In a therapeutic drug monitoring setting (trial II), 47 patients on doses ranging from 4 to 16 mg daily, including much polypharmacy, trough level steady-state serum samples were analyzed by the same bioanalytical method. Data from trials I and II were assessed to determine the inter- and intraindividual pharmacokinetic outcomes. The results showed that the median S,S/R,R ratio in steady state was 0.5 and ranged from 0.22 to 0.88. It was also shown that women have an approximately 30% higher S,S/R,R ratio than men. The S,S/R,R ratios of reboxetine were not found to correlate with reboxetine concentrations. To investigate the NARI activity of a circulating serum reboxetine concentration, a recalculation of the determined enantiomeric concentrations to previously demonstrated experimental NARI potencies of the drug enantiomers was performed. This partly novel concept of estimating pharmacodynamic activity showed that the serum NARI activity in women tended to be higher than in men at a given reboxetine concentration. In conclusion, the variability in the NARI activity per nmol/L reboxetine and the variability in the concentration outcome of the reboxetine enantiomers may justify the use of enantioselective drug monitoring in the clinic. The gender aspects of the drug have to be further assessed.

  • 197.
    Öhman, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    On-line extraction using an alkyl-diol silica precolumn for racemic citalopram and its metabolites in plasma: results compared with solid-phase extraction methodology2001Inngår i: Journal of Chromatography B: Biomedical Sciences and Applications, ISSN 1387-2273, E-ISSN 1878-5603, Vol. 753, nr 2, s. 365-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sample preparation is usually the most critical and time consuming step when using HPLC for drug analysis in biological matrixes. Sample extracts have to be clean considering both chromatographic interferences and column maintenance. To meet some of these criteria a fully automated on-line extraction (OLE) analysis method was developed for the antidepressant drug citalopram and its two demethylated metabolites, using an RP-C4-ADS extraction column. A comparison between the new OLE method and an off-line solid-phase extraction method showed that the two methodologies were equal in analytical precision but that the OLE method was faster and therefore superior in sample capacity per day.

  • 198.
    Öhman, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC2001Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 23, nr 1, s. 27-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reboxetine isa new antidepressant drug acting as a potent and selective noradrenaline reuptake inhibitor on the noradrenergic neuronal system. Because of an expected interindividual variability in drug metabolism in the clinical practice the need for therapeutic drug monitoring routines in psychiatry is always a prominent feature. In this application, the preferred bioanalytic methodology was solid phase extraction combined with reversed-Phase high-Performance liquid chromatography and ultraviolet detection at 210 nm. The technique proved reliable, with interday and intraday variation of less than 5% and a quantification limit for reboxetine and one of its main metabolites O-Desethylreboxetine (O-Reboxetine) at 5 and 30 nmol/L, respectively. The method was applied on serum samples from 38 patients treated chronically with reboxetine. These samples were drawn as trough levels in steady state with a dosage range of 2-16 mg/day. They evidenced a mean reboxetine concentration that was fairly linear and dose proportional, although the variance in concentration was large between patients, even those taking the same dosage. O-Reboxetine was detected in quantifiable amounts in only 1 of the 38 patients (<3%). In conclusion, these results suggest that a routine reboxetine therapeutic drug monitoring service that is robust enough to produce reliable and reproducible results may be introduced into everyday clinical practice.

  • 199.
    Öhman, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Simultaneous determination of reboxetine and O-desethylreboxetine enantiomers using enantioselective reversed-phase high-performance liquid chromatography2002Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 947, nr 2, s. 247-254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Current knowledge of stereoselective pharmacokinetics and different potencies of drug enantiomers requires the performance of stereoselective analysis during therapeutic drug monitoring in clinical practice. However, in the case of the new antidepressant drug reboxetine, no effort has been made so far to find a such a suitable system. Therefore, as a step towards developing an enantioselective bioanalytical method for reboxetine and the O-desethylreboxetine metabolite, three stereoselective chromatographic approaches have been investigated. Several chiral columns were tested, among them Chiral-AGP, ChiraGrom 2 and Chiral-CBH, which were able to simultaneously separate the two compounds into enantiomers in total running times of 28, 18 and 12 min, respectively.

  • 200.
    Öhman, Daniel
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Development of a TDM-Method for determination of the neuroleptic compound Ziprasidone and its S-methylated main metabolite.2001Inngår i: Pharmacol Toxicol,2001, 2001, s. 133-133Konferansepaper (Fagfellevurdert)
1234 151 - 200 of 200
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