Journal article
Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients.
- Rotger M Institute of Microbiology and Section of Infectious Diseases, University Hospital, Lausanne, Switzerland.
- Colombo S
- Furrer H
- Bleiber G
- Buclin T
- Lee BL
- Keiser O
- Biollaz J
- Décosterd L
- Telenti A
- 2005-05-03
Published in:
- Pharmacogenetics and genomics. - 2005
Adult
Alleles
Anti-HIV Agents
Aryl Hydrocarbon Hydroxylases
Benzoxazines
Cytochrome P-450 CYP2B6
Female
Genotype
HIV Infections
HIV Seropositivity
Humans
Leukocytes, Mononuclear
Male
Middle Aged
Nevirapine
Odds Ratio
Oxazines
Oxidoreductases, N-Demethylating
Pharmacogenetics
Polymorphism, Genetic
Protein Isoforms
Regression Analysis
Time Factors
English
BACKGROUND
Efavirenz (EFV) and nevirapine (NVP) are metabolized by cytochrome P450 2B6 (CYP2B6). Allele 516 G>T (Gln172His) is associated with diminished activity of this isoenzyme, and may lead to differences in drug exposure.
METHODS
We evaluated this allele as a pharmacogenetic marker of EFV and NVP pharmacokinetics and EFV toxicity in 167 participants receiving EFV and 59 receiving NVP recruited within the genetics project of the Swiss HIV Cohort Study. Drug concentrations were measured in plasma and in peripheral blood mononuclear cells (PBMCs) from the same sample. Neuropsychological toxicity of EFV (sleep disorders, mood disorders, fatigue) was assessed using a standardized questionnaire.
RESULTS AND CONCLUSIONS
CYP2B6 516TT was associated with greater plasma and intracellular exposure to EFV, and greater plasma exposure to NVP. Intracellular drug concentration, and CYP2B6 genotype were predictors of EFV neuropsychological toxicity. CYP2B6 genotyping may be useful to complement an individualization strategy based on plasma drug determinations to increase the safety and tolerability of EFV.
Efavirenz (EFV) and nevirapine (NVP) are metabolized by cytochrome P450 2B6 (CYP2B6). Allele 516 G>T (Gln172His) is associated with diminished activity of this isoenzyme, and may lead to differences in drug exposure.
METHODS
We evaluated this allele as a pharmacogenetic marker of EFV and NVP pharmacokinetics and EFV toxicity in 167 participants receiving EFV and 59 receiving NVP recruited within the genetics project of the Swiss HIV Cohort Study. Drug concentrations were measured in plasma and in peripheral blood mononuclear cells (PBMCs) from the same sample. Neuropsychological toxicity of EFV (sleep disorders, mood disorders, fatigue) was assessed using a standardized questionnaire.
RESULTS AND CONCLUSIONS
CYP2B6 516TT was associated with greater plasma and intracellular exposure to EFV, and greater plasma exposure to NVP. Intracellular drug concentration, and CYP2B6 genotype were predictors of EFV neuropsychological toxicity. CYP2B6 genotyping may be useful to complement an individualization strategy based on plasma drug determinations to increase the safety and tolerability of EFV.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/01213011-200501000-00001
- PMID 15864119
- Persistent URL
- https://sonar.ch/global/documents/189620
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