Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients

Détails

ID Serval
serval:BIB_664B41A07499
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients
Périodique
Pharmacogenetics and Genomics
Auteur(s)
Rotger  M., Colombo  S., Furrer  H., Bleiber  G., Buclin  T., Lee  B. L., Keiser  O., Biollaz  J., Decosterd  L., Telenti  A.
ISSN
1744-6872 (Print)
Statut éditorial
Publié
Date de publication
01/2005
Volume
15
Numéro
1
Pages
1-5
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
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.
Mots-clé
Adult Alleles Anti-HIV Agents/pharmacology Aryl Hydrocarbon Hydroxylases/*genetics Female Genotype HIV Infections/*drug therapy/*genetics HIV Seropositivity Humans Leukocytes, Mononuclear/metabolism Male Middle Aged Nevirapine/*pharmacology Odds Ratio Oxazines/*pharmacology Oxidoreductases, N-Demethylating/*genetics Pharmacogenetics *Polymorphism, Genetic Protein Isoforms Regression Analysis Time Factors
Pubmed
Création de la notice
25/01/2008 11:41
Dernière modification de la notice
03/03/2018 17:53
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