Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals.

Détails

ID Serval
serval:BIB_09C3908EC60D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals.
Périodique
Clinical Pharmacology and Therapeutics
Auteur(s)
Arab-Alameddine M., Di Iulio J., Buclin T., Rotger M., Lubomirov R., Cavassini M., Fayet A., Décosterd L.A., Eap C.B., Biollaz J., Telenti A., Csajka C.
ISSN
1532-6535[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
85
Numéro
5
Pages
485-494
Langue
anglais
Résumé
Besides CYP2B6, other polymorphic enzymes contribute to efavirenz (EFV) interindividual variability. This study was aimed at quantifying the impact of multiple alleles on EFV disposition. Plasma samples from 169 human immunodeficiency virus (HIV) patients characterized for CYP2B6, CYP2A6, and CYP3A4/5 allelic diversity were used to build up a population pharmacokinetic model using NONMEM (non-linear mixed effects modeling), the aim being to seek a general approach combining genetic and demographic covariates. Average clearance (CL) was 11.3 l/h with a 65% interindividual variability that was explained largely by CYP2B6 genetic variation (31%). CYP2A6 and CYP3A4 had a prominent influence on CL, mostly when CYP2B6 was impaired. Pharmacogenetics fully accounted for ethnicity, leaving body weight as the only significant demographic factor influencing CL. Square roots of the numbers of functional alleles best described the influence of each gene, without interaction. Functional genetic variations in both principal and accessory metabolic pathways demonstrate a joint impact on EFV disposition. Therefore, dosage adjustment in accordance with the type of polymorphism (CYP2B6, CYP2A6, or CYP3A4) is required in order to maintain EFV within the therapeutic target levels.
Pubmed
Web of science
Création de la notice
27/04/2009 15:20
Dernière modification de la notice
20/08/2019 12:31
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