Optimizing drug therapy during pregnancy: a spotlight on population pharmacokinetic modeling

INTRODUCTION: Optimizing drug therapy during pregnancy is crucial for ensuring the safety of mothers and babiesPhysiological changes that occur during pregnancy can significantly alter the pharmacokinetics of medications. Population pharmacokinetic (PopPK) modeling is a valuable tool to guide drug dosing regimens in pregnant women. AREAS COVERED: This narrative review summarizes the current literature on the application of PopPK modeling to optimize drug therapy during human pregnancy. It provides an overview of the physiological changes affecting drug disposition in pregnancy and the basic concepts of PopPK modeling including structural, stochastic, and covariate models. We have conducted an exhaustive literature search (PubMed, Web of Science) spanning May 2014-May 2024 to identify PopPK models in the pregnant population. We have highlighted strategies for model building, evaluation, and interpretation with a focus on identifying clinically relevant covariates that inform dose individualization. Case studies illustrating the utility of PopPK models in guiding dosing recommendations for specific drugs are discussed. EXPERT OPINION: Covariate identification can lead to improved mechanistic understanding of drug disposition and establishment of improved dosing regimens during pregnancy. Insufficient data across trimesters may limit the ability of PopPK models to capture time-varying gestational effects.