Maïlys De Sousa Mendes, Deborah Hirt, Saik Urien, Cécile Vinot, Elodie Valade, Claire Pressiat, Naïm Bouazza, Frantz Foissac, Stephane Blanche, Jean-Marc Treluyer, Sihem Benaboud
1 EA08 : Evaluation des thérapeutiques et pharmacologie périnatale et pédiatrique, Unité de recherche clinique Paris centre, 75006 Paris, France
Objectives: Pregnant women can be exposed to numerous drugs during the gestational period. Due to obvious ethical reason in vivo studies of foetal exposure to these drugs are limited and information about transplacental transfer prior administration to pregnant women would be highly desirable. This study presents a novel approach to quantitatively predict the fetal exposure of drugs administered to the mother.
Methods: We implemented transplacental parameters values estimated from the ex-vivo human placenta perfusion model in pregnancy-Physiologically Based PharmacoKinetic (p-PBPK) models in order to predict foetal PK profile. With our models we simulated foetal PK for 3 antiretroviral drugs, tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and lamivudine (3TC). We compared these predictions to observed cord blood plasma concentrations to support the validity of our models.
Results: Simulated foetal PK profiles were in accordance with observed cord concentrations. Moreover sensitivity analyse showed that foetal predictions were sensitive to changes in values of transplacental parameters obtained by the ex-vivo model.
Conclusions: The human placental perfusion study associated with PBPK analysis may be a new approach for predicting human foetal exposure
Reference: PAGE 24 () Abstr 3510 [www.page-meeting.org/?abstract=3510]
Poster: Drug/Disease modeling - Absorption & PBPK