Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients

Autor: Aurélie Barrail-Tran, Bernard Vrijens, Radojka M. Savic, F Mentré, Nembot G, Céline Verstuyft, Xavière Panhard, Diane Descamps, Xavier Duval, Cécile Goujard, Anne-Marie Taburet
Přispěvatelé: Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique moléculaire, pharmacogénétique et hormonologie, AARDEX Group, Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, the ANRS 134 - COPHAR 3 study group, Comets, Emmanuelle, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), University of California [San Francisco] (UCSF), University of California-University of California, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Pyridines
MESH: Drug Interactions
HIV Infections
Pharmacology
Deoxycytidine
030226 pharmacology & pharmacy
MESH: Genotype
0302 clinical medicine
immune system diseases
Cytochrome P-450 CYP3A
Emtricitabine
Drug Interactions
Pharmacology (medical)
Population pharmacokinetics
[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
MESH: Aged
MESH: Cytochrome P-450 CYP3A
0303 health sciences
MESH: Middle Aged
[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
virus diseases
MESH: HIV Infections
Middle Aged
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
3. Good health
MESH: Nonlinear Dynamics
MESH: Young Adult
MESH: Oligopeptides
Drug Therapy
Combination
Female
Oligopeptides
MESH: Organophosphonates
medicine.drug
Adult
MESH: Adenine
Genotype
Atazanavir Sulfate
Organophosphonates
MESH: Pharmacogenetics
Models
Biological
Article
Medication Adherence
Atazanavir
Young Adult
03 medical and health sciences
Pharmacotherapy
Pharmacokinetics
medicine
Humans
Dosing
Tenofovir
Alleles
Aged
MESH: HIV Protease Inhibitors
Ritonavir
MESH: Humans
030306 microbiology
business.industry
Adenine
MESH: Alleles
MESH: Pyridines
MESH: Deoxycytidine
MESH: Models
Biological
MESH: Adult
HIV Protease Inhibitors
MESH: Medication Adherence
MESH: Male
MESH: Drug Therapy
Combination
Nonlinear Dynamics
Adherence
Pharmacogenetics
MESH: Ritonavir
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
business
human activities
MESH: Female
Zdroj: Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics, 2012, 92 (5), pp.575-83. ⟨10.1038/clpt.2012.137⟩
Clinical Pharmacology and Therapeutics, American Society for Clinical Pharmacology and Therapeutics, 2012, 92 (5), pp.575-83. ⟨10.1038/clpt.2012.137⟩
ISSN: 0009-9236
1532-6535
Popis: International audience; 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.
Databáze: OpenAIRE
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