| Pharmacokinetic Variability of Quetiapine and the Active Metabolite N-desalkylquetiapine in Psychiatric Patients. | |
| | |
MedLine Citation:
|
PMID: 21383647 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
BACKGROUND:: Quetiapine is an atypical antipsychotic drug that was recently also approved for the treatment of uni- and bipolar depression. The antidepressive response is considered to be mediated by the metabolite N-desalkylquetiapine, and the aim of this study was to assess the interindividual pharmacokinetic variability of quetiapine and N-desalkylquetiapine in psychiatric patients based on therapeutic drug monitoring samples. METHODS:: Serum measurements of quetiapine and N-desalkylquetiapine performed between October 2007 and July 2008 were retrospectively included from a routine therapeutic drug monitoring database. Pharmacokinetic variability was expressed as the 5-95 percentile range in dose-adjusted serum concentrations (C/D ratios). The impact of age (65 years or older), gender, and sampling time on the C/D ratios was studied by linear mixed model analysis. Samples from patients comedicated with CYP3A4 inducers or inhibitors were examined separately. RESULTS:: In total, 927 serum samples from 601 patients were included (all using quetiapine immediate-release tablets). The 5-95 percentiles of the C/D ratio ranged 15-fold (0.14-2.1 nmol/L/mg) for quetiapine and fivefold (0.44-2.1 nmol/L/mg) for N-desalkylquetiapine. Elderly (65 years or older) obtained 1.5- and 1.2-fold higher C/D ratios of quetiapine (P = 0.002) and N-desalkylquetiapine (P = 0.03) compared with younger patients, respectively. Sampling time was also found to significantly affect the C/D ratios of quetiapine (P = 0.001), whereas gender was not a significant variable (P > 0.13). In three patients treated with potent CYP3A4 inducers, the observed C/D ratios of quetiapine and N-desalkylquetiapine were 77% and 11% lower than the mean C/D ratio in the study population, respectively. CONCLUSION:: The pharmacokinetic variability was greater for quetiapine compared with N-desalkylquetiapine. Age 65 years or older and comedication with CYP3A4 inducers affected the serum levels of both agents, but the relative impact was greater on quetiapine. |
| | |
Authors:
|
Gry Vibeke Bakken; Ida Rudberg; Espen Molden; Helge Refsum; Monica Hermann |
Related Documents
:
|
1454147 - Proton nmr spectroscopy of canavan's disease. 16896547 - Extent of atherosclerosis and prognosis of patients with aneurysmal subarachnoid haemor... 7071717 - Angiographically occult vascular malformations causing intracranial hemorrhage. 14339297 - Diazepam: a preliminary study of its effects on patients with athetoid cerebral palsy. 15981687 - Bilateral sacral radiculopathy in a cyclist. 15175797 - Plasma homocysteine concentration is not associated with activated protein c resistance... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-3-04 |
Journal Detail:
|
Title: Therapeutic drug monitoring Volume: - ISSN: 1536-3694 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2011-3-8 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7909660 Medline TA: Ther Drug Monit Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
From the *Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; and †Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Simulation to Assess the Safety of New Healthcare Teams and New Facilities.
Next Document: Simultaneous Determination of Antidementia Drugs in Human Plasma for Therapeutic Drug Monitoring.