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Journal articles
Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients.
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.
Cited literature [24 references]
https://www.hal.inserm.fr/inserm-00747884
Contributor : Emmanuelle Comets Connect in order to contact the contributor
Submitted on : Wednesday, April 3, 2013 - 7:00:11 AM
Last modification on : Thursday, June 17, 2021 - 3:46:54 AM
Long-term archiving on: : Thursday, July 4, 2013 - 2:33:10 AM
Contributor : Emmanuelle Comets Connect in order to contact the contributor
Submitted on : Wednesday, April 3, 2013 - 7:00:11 AM
Last modification on : Thursday, June 17, 2021 - 3:46:54 AM
Long-term archiving on: : Thursday, July 4, 2013 - 2:33:10 AM
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