Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments.

ABSTRACT:

Background and objective

Doravirine is currently not recommended for pregnant women living with human immunodeficiency virus because efficacy and safety data are lacking. This study aimed to predict maternal and fetal doravirine exposure by integrating human placenta perfusion experiments with pregnancy physiologically based pharmacokinetic (PBPK) modeling.

Methods

Ex vivo placenta perfusions were performed in a closed-closed configuration, in both maternal-to-fetal and fetal-to-maternal directions (n = 8). To derive intrinsic placental transfer parameters from perfusion data, we developed a mechanistic placenta model. Next, we developed a maternal and fetal full-body pregnancy PBPK model for doravirine in Simcyp, which was parameterized with the derived intrinsic placental

SUBMITTER: Bukkems VE 

PROVIDER: S-EPMC9349081 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature