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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
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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.
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