| Effect of Adherence as Measured by MEMS, Ritonavir Boosting, and CYP3A5 Genotype on Atazanavir Pharmacokinetics in Treatment-Naive HIV-Infected Patients. | |
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MedLine Citation:
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PMID: 23033116 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Clinical Pharmacology & Therapeutics (2012); advance online publication 3 October 2012. doi:10.1038/clpt.2012.137. |
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Authors:
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R M Savic; A Barrail-Tran; X Duval; G Nembot; X Panhard; D Descamps; C Verstuyft; B Vrijens; A-M Taburet; C Goujard; F Mentré |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-03 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: - ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Université Paris Diderot, Sorbonne Paris Cité, INSERM, UMR 738, Paris, France [2] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. |
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