Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals.

Détails

ID Serval
serval:BIB_6052FCB27C8D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Arab-Alameddine M., Fayet-Mello A., Lubomirov R., Neely M., di Iulio J., Owen A., Boffito M., Cavassini M., Günthard H.F., Rentsch K., Buclin T., Aouri M., Telenti A., Decosterd L.A., Rotger M., Csajka C.
Collaborateur(s)
Swiss HIV Cohort Study Group
Contributeur(s)
Battegay M., Bernasconi E., Böni J., Bucher H., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux C., Gorgievski M., Günthard H., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Karrer U., Kind C., Klimkai T., Ledergerber B., Martinetti G., Müller N., Nadal D., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., de Tejada B., Taffé P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2012
Volume
56
Numéro
6
Pages
2959-2966
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The objectives of this study were to characterize raltegravir (RAL) population pharmacokinetics in HIV-positive (HIV(+)) and healthy individuals, identify influential factors, and search for new candidate genes involved in UDP glucuronosyltransferase (UGT)-mediated glucuronidation. The pharmacokinetic analysis was performed with NONMEM. Genetic association analysis was performed with PLINK using the relative bioavailability as the phenotype. Simulations were performed to compare once- and twice-daily regimens. A 2-compartment model with first-order absorption adequately described the data. Atazanavir, gender, and bilirubin levels influenced RAL relative bioavailability, which was 30% lower in HIV(+) than in healthy individuals. UGT1A9*3 was the only genetic variant possibly influencing RAL pharmacokinetics. The majority of RAL pharmacokinetic variability remains unexplained by genetic and nongenetic factors. Owing to the very large variability, trough drug levels might be very low under the standard dosing regimen, raising the question of a potential relevance of therapeutic drug monitoring of RAL in some situations.
Mots-clé
Adolescent, Adult, Aged, Anti-HIV Agents, Female, Genotype, HIV Infections/drug therapy, HIV Infections/genetics, Humans, Male, Middle Aged, Models, Statistical, Models, Theoretical, Pharmacogenetics/methods, Ritonavir/pharmacology, Ritonavir/therapeutic use, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/09/2012 18:01
Dernière modification de la notice
20/08/2019 14:17
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