Elodie Valade (1) (2), Saïk Urien (1) (2), Floris Fauchet (1) (2), Naïm Bouazza (2), Frantz Foissac (2), Sihem Benaboud (3), Déborah Hirt (1) (2) (3), Jean-Marc Tréluyer (1) (2) (3)
(1) Université Paris Descartes, Sorbonne Paris Cité, EA 3620 (2) Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France (3) Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France
Objectives: The aim of this study was to describe the pharmacokinetics of emtricitabine (FTC) in a large population of HIV-1-infected adults, and to assess patient characteristics influencing the pharmacokinetics of emtricitabine.
Methods: Ambulatory HIV-1 positive patients taking a FTC-containing regimen were included. The data were analyzed using the nonlinear mixed-effect modeling software program Monolix version 4.1.3. The influence of covariates (sexe, body weight, age, cotreatments) on the pharmacokinetic parameters of FTC was explored.Thanks to Bayesian estimation of the parameters, drug exposure (AUC), maximal and minimal FTC concentrations were obtained for each individual.
Results: From 282 patients, 366 plasma FTC concentrations were available. The FTC pharmacokinetics was best described by a two-compartment model with linear absorption and elimination. The mean population parameter estimates (inter-patient variability) were 1.0 h-1 for the absorption rate constant; 14.3 L/h (18.3%) and 3.6 L/h for the apparent elimination and intercompartmental clearances; 60.2 L and 54.6 L for the apparent central and peripheral volumes of distribution. FTC apparent elimination clearance increased significantly with body weight. The median population AUC and the maximal and minimal FTC concentrations were respectively 13.5mg.h/L, 2.06 and 0.086 mg/L.
Conclusions: This is the first population-model describing the FTC pharmacokinetic profile in HIV-infected adults. The influence of body weight on the clearance explains a part of the inter-patient variability.
Â
Reference: PAGE 22 () Abstr 2784 [www.page-meeting.org/?abstract=2784]
Poster: Infection