Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism.

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Publication year
2006Source
British Journal of Clinical Pharmacology, 61, 2, (2006), pp. 148-54ISSN
Publication type
Article / Letter to editor

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Organization
Clinical Pharmacy
Internal Medicine
Former Organization
F.C. Donders Centre for Cognitive Neuroimaging
Journal title
British Journal of Clinical Pharmacology
Volume
vol. 61
Issue
iss. 2
Page start
p. 148
Page end
p. 54
Subject
CTR 2: Clinical Pharmacology and physiology; EBP 3: Effective Primary Care and Public Health; N4i 2: Invasive mycoses and compromised host; N4i 3: Poverty-related infectious diseases; NCEBP 13: Infectious diseases and international health; UMCN 3.2: Cognitive neurosciences; UMCN 4.1: Microbial pathogenesis and host defenseAbstract
AIMS: To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz. METHODS: Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR-restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity. RESULTS: A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration (<1.0 mg l(-1)) and 48 (18.9%) a toxic efavirenz concentration (>4.0 mg l(-1)). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism. CONCLUSIONS: Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz-induced toxicity in females and non-Caucasian patients.
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- Faculty of Medical Sciences [89180]
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