Elodie Valade (1) (2), Saïk Urien (1) (2), Floris Fauchet (1) (2), 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 aims of this study were to describe the pharmacokinetics of emtricitabine (FTC) in a large population of HIV-1-infected pregnant women and to assess the impact of pregnancy on the pharmacokinetics of this drug.
Methods: HIV-positive pregnant women, women at labor and non-pregnant women taking FTC as part of their therapeutic regimen were included. The data were analyzed using the nonlinear mixed-effect modeling software program Monolix version 4.1.3. Thanks to individual pharmacokinetic parameters, drug exposure (AUC) and minimal concentrations were obtained for each woman.
Results: A total of 457 plasma FTC concentrations from 103 non-pregnant, 46 pregnant women and 48 women at labor were available. The FTC pharmacokinetics was best described by a two-compartment model with linear absorption and elimination. The population parameter estimates (inter-patient variability) were 0.616 h-1 (0.503) for the absorption rate constant; 22.3 L/h (0.151) and 5.89 L/h for the apparent elimination and intercompartmental clearances; 100 L and 76.1 L for the apparent central and peripheral volumes of distribution. FTC apparent elimination clearance increased significantly with creatinine clearance, reflecting renal function. Median AUC0-24 in pregnant women (8.30 mg.h/L) was significantly different from the one in non-pregnant women (9.77 mg.h/L) (p < 0.01). Pregnant women FTC exposures were not significantly different between trimesters of pregnancy or labor.
Conclusions: This is the first population-model describing FTC pharmacokinetics during pregnancy. Our study shows for the first time that FTC exposures differences between pregnant and non-pregnant women previously described by classical approach [1,2] can be explained by a modified renal function during pregnancy. As FTC exposure decrease during pregnancy was estimated at 15 %, dosing adjustment during pregnancy does not appear to be necessary.
References:
[1] Colbers APH, Hawkins DA, Gingelmaier A, Kabeya K, Rockstroh JK, Wyen C, et al. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. AIDS Lond Engl. 13 mars 2013;27(5):739‑748.
[2] Stek AM, Best BM, Luo W, Capparelli E, Burchett S, Hu C, et al. Effect of pregnancy on emtricitabine pharmacokinetics. HIV Med. avr 2012;13(4):226‑235.
Reference: PAGE 23 (2014) Abstr 3081 [www.page-meeting.org/?abstract=3081]
Poster: Drug/Disease modeling - Infection