Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients
| Autor: | Gabriela Bleiber, Olivia Keiser, Thierry Buclin, Amalio Telenti, Laurent A. Decosterd, Belle L. Lee, Hansjakob Furrer, Margalida Rotger, Sara Colombo, Jérôme Biollaz |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Cyclopropanes Male Time Factors Efavirenz Nevirapine Genotype CYP2B6 Anti-HIV Agents HIV Infections Biology Pharmacology chemistry.chemical_compound Pharmacokinetics immune system diseases HIV Seropositivity Oxazines Odds Ratio Genetics medicine Humans Protein Isoforms General Pharmacology Toxicology and Pharmaceutics Molecular Biology Alleles Genetics (clinical) Polymorphism Genetic Reverse-transcriptase inhibitor virus diseases Oxidoreductases N-Demethylating Middle Aged Benzoxazines Cytochrome P-450 CYP2B6 chemistry Tolerability Pharmacogenetics Alkynes Toxicity Leukocytes Mononuclear Regression Analysis Molecular Medicine Female Aryl Hydrocarbon Hydroxylases medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 15:1-5 |
| ISSN: | 1744-6872 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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