We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effect of Adherence as Measured by MEMS, Ritonavir Boosting, and CYP3A5 Genotype on Atazanavir Pharmacokinetics in Treatment-Naive HIV-Infected Patients.
- Authors
Savic, R M; Barrail-Tran, A; Duval, X; Nembot, G; Panhard, X; Descamps, D; Verstuyft, C; Vrijens, B; Taburet, A-M; Goujard, C; Mentré, F
- Abstract
We investigated population pharmacokinetics and pharmacogenetics of ritonavir-boosted atazanavir (ATV), using drug intake times exactly recorded by the Medication Event Monitoring System. The ANRS 134-COPHAR 3 trial was conducted in 35 HIV-infected treatment-naive patients. ATV (300 mg), ritonavir (100 mg), and tenofovir (300 mg) + emtricitabine (200 mg), in bottles with MEMS caps, were taken once daily for 6 months. Six blood samples were collected at week 4 to measure drug concentrations, and trough levels were measured bimonthly. A model integrating ATV and ritonavir pharmacokinetics and pharmacogenetics used nonlinear mixed effects. Use of exact dosing data halved unexplained variability in ATV clearance. The ritonavir-ATV interaction model suggested that optimal boosting effect is achievable at lower ritonavir exposures. Patients with at least one copy of the CYP3A5*1 allele exhibited 28% higher oral clearance. We provide evidence that variability in ATV pharmacokinetics is defined by adherence, CYP3A5 genotype, and ritonavir exposure.
- Subjects
THERAPEUTICS; HIV infections; PATIENT compliance; RITONAVIR; PHARMACOGENOMICS; PHARMACOKINETICS; EMTRICITABINE; ORAL drug administration; PHARMACODYNAMICS
- Publication
Clinical Pharmacology & Therapeutics, 2012, Vol 92, Issue 5, p575
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2012.137