Pregnancy-Related Effects on Tenofovir Pharmacokinetics: a Population Study with 186 Women

Autor: Saik Urien, Sihem Benaboud, Frantz Foissac, Jean-Marc Tréluyer, Elisabeth Rey, Hélène Chappuy, Naïm Bouazza, Odile Launay, Emmanuelle Pannier, Ghislaine Firtion, Déborah Hirt
Rok vydání: 2012
Předmět:
Zdroj: Antimicrobial Agents and Chemotherapy. 56:857-862
ISSN: 1098-6596
0066-4804
DOI: 10.1128/aac.05244-11
Popis: According to the European AIDS Clinical Society, tenofovir disoproxil fumarate can be used in HIV-infected pregnant women if started prior to pregnancy, although no data are available on the pharmacokinetics of tenofovir (TFV) during pregnancy. The aim of this study was to describe TFV pharmacokinetics in HIV-infected women and to evaluate the effect of pregnancy on TFV disposition. Samples were collected according to a therapeutic drug monitoring in 186 women, including 46 pregnant women treated with TFV and retrospectively analyzed by a population approach. TFV pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. The mean population parameter estimates (between-subject variability) were as follows: absorption rate constant, 0.56 h −1 ; elimination clearance, 59.9 liters h −1 (0.436); central volume of distribution, 552 liters (1.96); intercompartmental clearance, 172 liters/h; and peripheral volume of distribution, 1,390 liters. Pregnant women had a 39% higher apparent clearance compared to nonpregnant women. Apparent clearance significantly decreased with age. In order to obtain an exposure similar to the known exposure in adults and guarantee similar trough concentrations ( C min ) as observed in adults, an increase in the TFV dose should be considered for women from the second trimester to delivery.
Databáze: OpenAIRE