Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Caffeine Disposition in Pregnancy

Caffeineis the most consumed active stimulant. About 80% of pregnant women consume caffeineorally on a daily basis. Many reports indicated consumption of >200 mg caffeineduring pregnancy could increase the likelihood of miscarriage. In this article, we developed a pregnancy physiological-based pharmacokinetic/pharmacodynamic (PBPK/PD) model for caffeineto examine association between maternal caffeineconsumption during pregnancy and caffeineplasma levels at doses lower and higher than 200 mg to predict changes in caffeineconcentrations across the 3 trimesters, and to predict associated changes in caffeinePD parameters. Two models were successfully developed using GastroPlus software, a nonpregnant model for validation purposes and a pregnant model for validation and prediction of maternal caffeineplasma concentrations following single and multiple dosing. Using observed and predicted data, we were able to validate and simulate PK changes of caffeinein nonpregnant women and the PD effect of caffei...