Physiologically-based pharmacokinetic models to predict drug exposure during pregnancy

As pregnant women are constantly exposed to drugs during pregnancy, either to treat long-term conditions or acute illnesses, drug safety is a major concern for the fetus and the mother. Clinical trials are rarely made in this population due to strict regulation and ethical reasons. However, drug pharmacokinetic (PK) parameters vary during pregnancy with an increase in distribution volume, renal clearance and more. In addition, the fetal distribution should be evaluated with the importance of placental diffusion, both active and passive. Therefore, there is a recent interest in the use of physiologically-based pharmacokinetic (PBPK) modeling to characterize these changes and complete the sparse data available on drug PK during pregnancy. Indeed, PBPK models integrate drug physicochemical and physiological parameters corresponding to each compartment of the body to estimate drug concentrations. This review establishes an overview on the current use of PBPK models in drug dosage determination for the pregnant woman, fetal exposure and drug interactions in the fetal compartment.