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  • 1.
    Carlsson, Björn
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Optimization and Characterization of the Chiral Separation of Citalopram and its Demethylated Metabolites by Response Surface Methodology2001Ingår i: Chromatographia, ISSN 0009-5893, Vol. 53, nr 5/6, s. 266-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Response-surface modelling and sequential optimization have been used for optimization and characterization of the separation of the enantiomers of citalopram, desmethylcitalopram, and didesmethylcitalopram on an acetylated ▀-cyclodextrin column. In the model chosen the separation conditions mobile phase methanol content, buffer concentration, column temperature, and pH were varied to investigate their influence on the chromatography. It was found that what is good for selectivity within an enantiomer pair is bad for selectivity between enantiomer pairs. Because within-pair and between-pair selectivity does not reach its optimum at the same conditions, a middle course approach has to be followed. Use of an experimental design for this investigation enabled understanding of the mechanisms of within- and between-pair separation for citalopram, desmethylcitalopram, and didesmethylcitalopram. Sequential optimization can be a quicker means of optimizing a chromatographic separation, response-surface modelling, in addition to enabling optimization of the chromatographic process, also serves as a tool for learning more about the separation mechanism.

  • 2.
    Carlsson, Björn
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Solid-phase extraction with end-capped C2 columns for the routine measurement of racemic citalopram and metabolites in plasma by high-performance liquid chromatography1997Ingår i: Journal of Chromatography B: Biomedical Sciences and Applications, ISSN 1570-0232, Vol. 702, nr 1-2, s. 234-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An assay based on solid-phase extraction followed by high-performance liquid chromatography (HPLC) was developed for the measurement of citalopram and its main metabolites desmethylcitalopram and didesmethylcitalopram. The best extraction procedure was performed with end-capped C2 column utilising secondary silanol interactions to obtain clean extract. The HPLC analysis was done on a phenyl column with a mobile phase without any amine additives. Fluorescence detection gave a limit of detection of 0.8 nmol/l plasma for the compounds analysed.

  • 3.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Kullman, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Jan-Edvin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Kågedal, Bertil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis1999Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 45, nr 10, s. 1813-1820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.

    Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.

    Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.

    Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

  • 4.
    Green, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Vretenbrant (Öberg), Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Measurement of paclitaxel and its metabolites in human plasma using liquid chromatography/ion trap mass spectrometry with a sonic spray ionization interface2006Ingår i: Rapid Communications in Mass Spectrometry, ISSN 1097-0231, Vol. 20, nr 14, s. 2183-2189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A quantitative liquid chromatography/ion trap mass spectrometry method for the simultaneous determination of paclitaxel, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel in human plasma has been developed and validated. 6α-,p-3'-Dihydroxypaclitaxel was also quantified using paclitaxel as a reference and docetaxel as an internal standard. The substances were extracted from 0.500 mL plasma using solid-phase extraction. The elution was performed with acetonitrile and the samples were reconstituted in the mobile phase. Isocratic high-performance liquid chromatography analysis was performed by injecting 50 µL of reconstituted material onto a 100 × 3.00 mm C12 column with a methanol:1% trifluoroacetic acid/ammonium trifluoroacetate in H2O 70:30 mobile phase at 350 µL/min. The [M+H]+ ions generated in the sonic spray ionization interface were isolated and fragmented using two serial mass spectrometric methods: one for paclitaxel (transition 854 → 569 & 551) and the dihydroxymetabolite (transition 886 → 585 & 567) and one for the hydroxy metabolites (transition 870 → 585 & 567; transition 870 → 569 & 551) and docetaxel ([M+Na]+, transition 830 → 550). Calibration curves were created ranging between 0.5 and 7500 ng/mL for paclitaxel, 0.5 and 750 ng/mL for 6α-hydroxypaclitaxel, and 0.5 and 400 ng/mL for p-3'-hydroxypaclitaxel. Adduct ion formation was noted and investigated during method development and controlled by mobile phase optimization. In conclusion, a sensitive method for simultaneous quantification of paclitaxel and its metabolites suitable for analysis in clinical studies was obtained.

  • 5.
    Gréen, Henrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Vretenbrandt, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Measurement of Paclitaxel and its metabolites in Human Plasma Using a Liquid Chromatography - Ion Trap Mass Spectrometer with a SSI interface2008Konferensbidrag (Refereegranskat)
  • 6.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying1997Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 53, nr 04-Mar, s. 241-246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To determine if treatment with low-dose aspirin (ASA) influences the bioavailability of orally administered alcohol and to assess whether this is caused by altered gastric emptying as measured by the paracetamol absorption test.

    Methods: In a single-center controlled crossover trial, ten healthy male medical students, aged 20–27 years, participated in two experiments in random order. Both times they took paracetamol (1.5 g together with a standardized breakfast) and drank ethanol (0.3 g/kg) 1 h after eating breakfast. On one drinking occasion, no previous medication was given. The other alcohol session was performed after the subjects had taken 75 mg ASA once daily for 7 days. On both occasions, venous blood samples were obtained at exactly timed intervals for a period of 3.5 h.

    Results: The blood-ethanol profiles showed large interindividual variations for both experiments. After treatment with ASA, the maximum blood-ethanol concentration was distinctly lower in seven subjects, almost unchanged in two subjects and increased in one subject. Overall, a statistically significant decrease in the peak blood-ethanol concentration was observed. The time required to reach peak blood-ethanol levels was somewhat longer after treatment with ASA. Although the areas under the concentration–time profiles were smaller after ASA treatment, these differences were not statistically significant. The concentrations of paracetamol in plasma were lower when ethanol was ingested after treatment with ASA and the areas under the concentration–time curves (0–170 min) were smaller.

    Conclusions: Intake of low-dose ASA (75 mg daily) tends to delay the absorption of a moderate dose of ethanol, which results in lower peak blood-ethanol concentrations and smaller areas under the concentration–time curves. The underlying mechanism seems to be delayed gastric emptying as indicated by the paracetamol absorption test.

  • 7.
    Larsby, Birgitta
    et al.
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Tham, Richard
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Ödkvist, Lars
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Norlander, Björn
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Hydén, Dag
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Aschan, Gunnar
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Rubin, A.
    Linköpings universitet. Department of Otolaryngology and Department of Clinical Pharmacology, Regional and University Hospital, Linköping University, Linköping, Sweden .
    Exposure of rabbits to methylchloroform. Vestibulardisturbances correlated to blood and cerebrospinal fluid levels1978Ingår i: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 41, nr 1, s. 7-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A previously described experimental model for studying the effects on the central nervous system of rabbits, specifically the vestibular apparatus, has been applied to methylchloroform. To achieve a steady concentration the solvent was infused as a lipid emulsion. The blood and cerebrospinal fluid kinetics have been studied. The arterial blood level seems to be closely correlated to the concentration in the central nervous tissue. Vestibular function has been studied by recording the involuntary eye movements — nystagmus — which are elicited via central vestibulo-oculomotor connections. At blood levels of methylchloroform above 75 ppm a so called “positional nystagmus”, indicated vestibular disturbances, is demonstrated. The relationship between the present findings in rabbits and the reaction and blood concentrations in people exposed to industrial solvents, are discussed.

  • 8.
    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 volunteers1999Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 13, nr 6, s. 1230-1235Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Tham, Richard
    et al.
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    Larsby, Birgitta
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    Ödkvist, Lars
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    Norlander, Björn
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    Hydén, Dag
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    Aschan, Gunnar
    Linköpings universitet. Departments of Otolaryngology and Clinical Pharmacology, Regional-and University Hospital, Linköping University, Linköping, Sweden.
    The influence of trichlorethylene and related drugs on the vestibular system1979Ingår i: Acta Pharmacologica et Toxicologica, ISSN 0001-6683, Vol. 44, nr 5, s. 336-342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A previously described experimental model for studying the effect of industrial solvents on the vestibular system of rabbits has been applied to trichloroethylene. Estimation of trichloroethylene and its metabolites in blood and cerebrospinal fluid was performed by gas chromatography. Vestibular function was studied by recording nystagmus, induced by positional changes or accelerated rotation. At blood levels of trichloroethylene above 30 p.p.m. “positional nystagmus” develops. Two metabolites of trichloroethylene, chloral hydrate and trichloro-ethanol, which are known as central nervous system (CNS) depressants, did not induce this abnormal nystagmus. However, α-chloralose, a derivative of chloral hydrate, induced positional nystagmus and also a markedly exaggerated nystagmus developed during rotatory acceleration. It is suggested that solvents like trichloroethylene elicit vestibular disturbances by stimulation of central subcortical vestibulo-oculomotor connections. The stimulation may be caused by a blockage of inhibitory systems.

  • 10.
    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 reboxetine2003Ingår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 174-182Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    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 methodology2001Ingår i: Journal of Chromatography B: Biomedical Sciences and Applications, ISSN 1387-2273, E-ISSN 1878-5603, Vol. 753, nr 2, s. 365-373Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    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 HPLC2001Ingår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 23, nr 1, s. 27-34Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    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 chromatography2002Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 947, nr 2, s. 247-254Artikel i tidskrift (Refereegranskat)
    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.

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