Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals.

Détails

ID Serval
serval:BIB_001364580150
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals.
Périodique
The Journal of antimicrobial chemotherapy
Auteur(s)
Barceló C., Gaspar F., Aouri M., Panchaud A., Rotger M., Guidi M., Cavassini M., Buclin T., Decosterd L.A., Csajka C.
Collaborateur(s)
Swiss HIV Cohort Study
Contributeur(s)
Aubert V., Battegay M., Bernasconi E., Böni J., Braun D., Bucher H., Burton-Jeangros C., Calmy A., Cavassini M., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux C., Gorgievski M., Günthard H., Haerry D., Hasse B., Hirsch H., Hoffmann M., Hösli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kouyos R., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Marzolini C., Metzner K., Müller N., Nadal D., Nicca D., Pantaleo G., Rauch A., Regenass S., Rudin C., Schöni-Affolter F., Schmid P., Speck R., Stöckle M., Tarr P., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Statut éditorial
Publié
Date de publication
07/2016
Peer-reviewed
Oui
Volume
71
Numéro
7
Pages
1933-1942
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Co-formulated elvitegravir, cobicistat, tenofovir disoproxil fumarate and emtricitabine is among the preferred regimens for first-line ART. A population approach was used to characterize the pharmacokinetics of elvitegravir and cobicistat and identify individual factors and co-medications influencing their disposition, taking into consideration the interaction between the two compounds.
The study population included 144 HIV-infected individuals who provided 186 and 167 elvitegravir and cobicistat plasma concentrations, respectively. First, distinct NONMEM(®) analyses were conducted for elvitegravir and cobicistat, including individual demographic, clinical and genetic factors as potential covariates. Elvitegravir and cobicistat interaction was then assessed through different inhibitory models. Simulations based on the final model served to compare expected drug concentrations under standard and alternative dosage regimens.
Clearance with between-subject variability was 7.6 L/h [coefficient of variation (CV) 16.6%] and volume of distribution 61 L for elvitegravir and 16.0 L/h (CV 41.9%) and 88.3 L, respectively, for cobicistat. Concomitant administration of non-ritonavir-boosted atazanavir decreased elvitegravir clearance by 35%, likely due to UDP-glucuronosyl transferase (UGT) 1A1 inhibition. Concomitant administration of non-ritonavir-boosted atazanavir and ritonavir-boosted darunavir decreased cobicistat clearance by 47% and 27%, respectively. The final interaction model included cobicistat exposure (AUC0-24) on elvitegravir clearance. Simulations confirmed that a reduced elvitegravir dose of 85 mg co-administered with cobicistat and atazanavir produces a concentration-time course comparable to the standard regimen without atazanavir.
Elvitegravir and cobicistat pharmacokinetic variability appears to be mainly explained by drug-drug interactions that may be encountered in routine clinical practice. In these cases, therapeutic drug monitoring and surveillance for potential toxicities would be justified.

Mots-clé
Adolescent, Adult, Aged, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/pharmacokinetics, Area Under Curve, Cobicistat/administration & dosage, Cobicistat/pharmacokinetics, Cohort Studies, Computer Simulation, Drug Interactions, Female, HIV Infections/drug therapy, HIV Infections/virology, HIV-1/isolation & purification, Humans, Male, Middle Aged, Models, Statistical, Quinolones/administration & dosage, Quinolones/pharmacokinetics, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/04/2016 17:48
Dernière modification de la notice
08/05/2019 13:37
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