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Therapeutic drug monitoring of sertraline: Variability factors as displayed in a clinical setting
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-6041-0744
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
2000 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 22, no 4, 446-454 p.Article in journal (Refereed) Published
Abstract [en]

This report describes sertraline pharmacokinetics derived from routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method with ultraviolet detection was established for routine sertraline TDM, and 924 analyses were performed from April 1995 to May 1997. Extensive predefined inclusion/exclusion criteria were applied to increase the validity of scientifically evaluated data. Subsequently, 605 samples (65.5%) were excluded. The remaining 319 samples from 319 patients, representative of steady state through specimens and accompanied by essential clinical information provided on request forms, were scrutinized. A pronounced interindividual variability was observed. Smokers had significantly lower concentration-to-dose (C/D) mean ratios of serum sertraline (s-sert) and its main metabolite desmethylsertraline (s-dsert) than nonsmokers. Higher s-sert and s-dsert C/D mean ratios were found in elderly patients than in adults aged less than 65 years. In a subset of 20 patients in whom repeated TDM analyses were performed, observed intraindividual sertraline TDM outcome variability was low. The results highlight sertraline TDM as a tool for individual dose optimization and evaluation of patient drug compliance as well as drug-drug interactions.

Place, publisher, year, edition, pages
2000. Vol. 22, no 4, 446-454 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27666DOI: 10.1097/00007691-200008000-00014Local ID: 12404OAI: oai:DiVA.org:liu-27666DiVA: diva2:248218
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-10-28Bibliographically approved
In thesis
1. Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age
Open this publication in new window or tab >>Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objective: The aim of the present thesis is to examine the pharmacokinetic and biochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in the elderly.

Background: Symptoms of depression are found in up to 15% of the elderly and the prevalence of major depression is reported to be about 3%. At present SSRIs are the pharmacological tools most frequently used for the treatment of depression. Patients in old age account for a relatively higher proportion of SSRI expenditures, although the elderly are seriously underrepresented in pharmacological studies and are increasingly susceptible to adverse drug events.

Subjects and Methods: Serum concentrations of the SSRis fluoxetine, paroxetine, and sertraline in the elderly were compared to those in younger patients. Effects of paroxetine on cerebrospinal fiuid (CSF) monoamine concentrations were investigated. Influences of therapeutic drug monitoring (TDM) of citalopram, paroxetine, and sertraline on clinical dosing strategies and antidepressant drug costs during a 6-9-month follow-up were studied in depressed elderly patients. Various individual factors, including age, which may influence serum concentrations of fluoxetine and sertraline were evaluated using population TOM data.

Results: lnterindividual serum concentration variations were pronounced irrespective of age. Compared to the variability between subjects, the intraindividual variability of fiuoxetine and sertraline serum concentrations was found to be low. In the elderly, fiuoxetine, paroxetine, and sertraline serum concentrations were higher than in younger patients. In the case of fluoxetine, gross obesity influenced serum concentrations and sertraline serum concentrations were lower in smokers than in non-smokers. In the case of paroxetine, nonlinear pharmacokinetics were observed in some subjects and paroxetine treatment influenced both serotonergic and noradrenergic neurotransmission, as indicated by 5-HIAA and MHPG concentrations in the CSF. TDM-supported SSRI clinical dosing was found to reduce the doses used and efficacy was sustained when observed during an open follow-up.

Conclusions: The results reported in the present thesis emphasize the importance of conducting clinical and pharmacological research in the elderly in different phases of drug development. In the postmarketing phase, TOM databases provide important tools for the collection of new pharmacokinetic data from clinical populations and data important for the interpretation of population SS RI serum concentrations. TDM of the SSRis may support individual dose optimization, including assessments of drug compliance.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 94 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 650
Keyword
Serum concentrations, cerebrospinal fluid, pharmacokinetics, selective serotonin reuptake inhibitors, therapeutic drug monitoring, elderly, depression, pharmaceutical economics
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28058 (URN)12821 (Local ID)91-7219-751-X (ISBN)12821 (Archive number)12821 (OAI)
Public defence
2000-11-24, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-15Bibliographically approved

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Lundmark, JönsReis, MargaretaBengtsson, Finn

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