1. Effect of Adherence as Measured by MEMS, Ritonavir Boosting, and CYP3A5 Genotype on Atazanavir Pharmacokinetics in Treatment-Naive HIV-Infected Patients.
- Author
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Savic, R M, Barrail-Tran, A, Duval, X, Nembot, G, Panhard, X, Descamps, D, Verstuyft, C, Vrijens, B, Taburet, A-M, Goujard, C, and Mentré, F
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THERAPEUTICS ,HIV infections ,PATIENT compliance ,RITONAVIR ,PHARMACOGENOMICS ,PHARMACOKINETICS ,EMTRICITABINE ,ORAL drug administration ,PHARMACODYNAMICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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