Physiologically Based Pharmacokinetic Modeling in Pregnant Women Suggests Minor Decrease in Maternal Exposure to Olanzapine.

ABSTRACT: Pregnancy is accompanied by significant physiological changes that might affect the in vivo drug disposition. Olanzapine is prescribed to pregnant women with schizophrenia, while its pharmacokinetics during pregnancy remains unclear. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of olanzapine in the pregnant population. With the contributions of each clearance pathway determined beforehand, a full PBPK model was developed and validated in the non-pregnant population. This model was then extrapolated to predict steady-state pharmacokinetics in the three trimesters of pregnancy by introducing gestation-related alterations. The model adequately simulated the reported time-concentration curves. The geometric mean fold error of C_max and AUC w

SUBMITTER: Zheng L 

PROVIDER: S-EPMC8807508 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature