Assessment of Maternal and Fetal Dolutegravir Exposure by Integrating Ex Vivo Placental Perfusion Data and Physiologically-Based Pharmacokinetic Modeling.

ABSTRACT: Antiretroviral therapy during pregnancy reduces the risk of vertical HIV-1 transmission. However, drug dosing is challenging as pharmacokinetics (PK) may be altered during pregnancy. We combined a pregnancy physiologically-based pharmacokinetic (PBPK) modeling approach with data on placental drug transfer to simulate maternal and fetal exposure to dolutegravir (DTG). First, a PBPK model for DTG exposure in healthy volunteers was established based on physiological and DTG PK data. Next, the model was extended with a fetoplacental unit using transplacental kinetics obtained by performing ex vivo dual-side human cotyledon perfusion experiments. Simulations of fetal exposure after maternal dosing in the third trimester were in accordance with clinically observed DTG cord blood data. Furthermor

SUBMITTER: Freriksen JJM 

PROVIDER: S-EPMC7325314 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature