Physiologically Based Pharmacokinetic Model of Midazolam Disposition during Pregnancy

摘要

Disposition of drugs in pregnant women is poorly understood in spite of widespread prescription of drugs to women during gestation. We have developed a whole body physiologically based pharmacokinetic (PBPK) model to explore the effects of pregnancy on pharmacokinetics. The model accounts for maternofetal changes over the course of gestation; physiological and drug-specific parameters are taken from literature. Here we preliminarily demonstrate the model's utility to predict midazolam pharmacokinetics following intravenous bolus dosing in women undergoing Caesarian section. Simulations of maternal venous plasma concentrations compare favorably with data extracted from historical studies.