Document Detail


Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients.
MedLine Citation:
PMID:  23033116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  92     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2012-12-27     Revised Date:  2014-03-13    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  575-83     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adenine / analogs & derivatives,  therapeutic use
Adult
Aged
Alleles
Cytochrome P-450 CYP3A / genetics*
Deoxycytidine / analogs & derivatives,  therapeutic use
Drug Interactions
Drug Therapy, Combination
Female
Genotype
HIV Infections / drug therapy*
HIV Protease Inhibitors / pharmacokinetics,  pharmacology,  therapeutic use
Humans
Male
Medication Adherence*
Middle Aged
Models, Biological
Nonlinear Dynamics
Oligopeptides / pharmacokinetics*,  therapeutic use
Organophosphonates / therapeutic use
Pharmacogenetics
Pyridines / pharmacokinetics*,  therapeutic use
Ritonavir / pharmacology*,  therapeutic use
Young Adult
Chemical
Reg. No./Substance:
0/HIV Protease Inhibitors; 0/Oligopeptides; 0/Organophosphonates; 0/Pyridines; 0/emtricitabine; 0W860991D6/Deoxycytidine; 107021-12-5/tenofovir; EC 1.14.14.1/CYP3A5 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A; JAC85A2161/Adenine; O3J8G9O825/Ritonavir; QZU4H47A3S/atazanavir
Investigator
Investigator/Affiliation:
A Barrail-Tran / ; A Brunet / ; M-J Commoy / ; S Couffin-Cadiergues / ; D Descamps / ; X Duval / ; C Goujard / ; C Le Guellec / ; F Mentré / ; G Nembot / ; A-M Taburet / ; B Vrijens / ; Ajana / ; Aissi / ; Baclet / ; Besnier / ; Bollens / ; Boulanger / ; Brochier / ; Brunet / ; Chaix / ; Ciuchete / ; Ghosn / ; Duval / ; Ferret / ; Ferret / ; Gaubin / ; Goujard / ; Girard / ; Kouadio / ; Lupin / ; Parienti / ; Parrinello / ; Poinçon de la Blanchardière / ; May / ; Marien / ; Medintzeff / ; Metivier / ; Mole / ; Molina / ; Nau / ; Ouazene / ; Pintado / ; Quertainmont / ; Ramani / ; Rami / ; Sellier / ; Simon / ; Talbi / ; Thoirain / ; Verdon / ; Trépo / ; Wassoumbou / ; Yazdanpanah / ; Barrail-Tran / ; Gagneux / ; Delhotal / ; Hoizey / ; Houdret / ; Leguellec / ; Peytavin / ; Poirier / ; Sauvageon / ; Taburet / ; André / ; Soulié / ; Calvez / ; Morand-Joubert / ; Harchi / ; Bocket / ; Mourez / ; Palmer / ; Pallier / ; Deschamps / ; Mazeron / ; Bolmann / ; Storto / ; Thanh Thuy / ; G Nembot / ; G Unal / ; F Mentré / ; F Mentré / ; X Panhard / ; R Savic / ; B Vrijens /
Comments/Corrections

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