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PII‐44
Author(s) -
Taburet A.,
BarrailTran A.,
Mentreé F.,
Piketty C.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.169
Subject(s) - atazanavir , pharmacokinetics , ritonavir , elimination rate constant , volume of distribution , population , medicine , renal function , dosing , pharmacology , chemistry , lopinavir , human immunodeficiency virus (hiv) , urology , viral load , antiretroviral therapy , virology , environmental health
AIM To analyze, in HIV‐1 infected patients (pts), the pharmacokinetics (PK) of combined atazanavir (ATV), low dose ritonavir (RTV) and tenofovir (TNF). METHODS 10 highly pretreated adults pts, who were included in the ANRS 107 trial, received OD ATV (300 mg), RTV (100 mg), TNF (300 mg) and NRTIs. Blood samples for ATV, RTV and TNF assays were drawn at week 6 prior to drug intake in the morning and 1, 2, 3, 5, 8 and 24 hours post dosing. The data were analyzed using a population approach (WinNonMix version 2.0.1 Pharsight) with the 1 st order method and parametrized with the volume of distribution (V/F), absorption and elimination rate constants. Clearance (Cl/F) and elimination half‐life (t1/2) were deduced. RESULTS A one‐compartment model with 1 st order rate of absorption (ka) and elimination was used to describe ATV and RTV PK. A two‐compartment model with zero order absorption (absorption time fixed at 1h) and 1 st order elimination was used for TNF. Tested covariates were age, weight, creatinine clearance (CrCl), bilirubine. Mean individual parameters (variability in CV%) were as follows: (See Table)ATV RTV TNFV/F (L) 91 (45%) 141 (71%) 1072 (23%), central Cl/F (L/h) 9.2 (44%) 19.5 (71%) 125 (43%) ka (1/h) 0.5 1.3T1/2 (h) 7.0 (18%) 5.5 (0.3%) 17.2 (50%), terminalThe only significant covariate effect was CrCl on the elimination rate constant of TNF (p=0.006). CONCLUSIONS This analysis provides PK parameters for ATV, RTV and TNF used in combination in HIV infected pts. Exposure during long term therapy will be analyzed using these models. Clinical Pharmacology & Therapeutics (2005) 79 , P47–P47; doi: 10.1016/j.clpt.2005.12.169