Title:Toward Greater Insights on Applications of Modeling and Simulation in Pregnancy
VOLUME: 21 ISSUE: 9
Author(s):Ling Song, Cheng Cui, Ying Zhou, Zhongqi Dong, Zhiheng Yu, Yifan Xu, Tianyan Zhou, Khaled Abduljalil, Hongcan Han, Li Li, Jinbo Yang, Yangyu Zhao*, Haiyan Li and Dongyang Liu*
Affiliation:Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, Drug Clinical Trial Center, Peking University Third Hospital, Beijing, Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, Clinical Pharmacology, Janssen (China) R&D Center, Shanghai, Drug Clinical Trial Center, Peking University Third Hospital, Beijing, Drug Clinical Trial Center, Peking University Third Hospital, Beijing, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, Certara UK Limited, Simcyp Division, Sheffield, Centre of Drug Evaluation, National Medical Products Administration, Beijing, Centre of Drug Evaluation, National Medical Products Administration, Beijing, Centre of Drug Evaluation, National Medical Products Administration, Beijing, Obstetrics, Peking University Third Hospital, Beijing, Drug Clinical Trial Center, Peking University Third Hospital, Beijing, Drug Clinical Trial Center, Peking University Third Hospital, Beijing
Keywords:Pregnancy, modeling-and-simulation, clinical trial, physiologically-based-pharmacokinetic, population-pharmacokinetic, exposure-
response analysis.
Abstract:Pregnant women are often excluded from routine clinical trials. Consequently, appropriate dosing
regimens for majority of drugs are unknown in this population, which may lead to unexpected safety issue or insufficient
efficacy in this un-studied population. Establishing evidence through the conduct of clinical studies in
pregnancy is still a challenge. In recent decades, physiologically-based pharmacokinetic (PBPK) modeling has
proven to be useful to support dose selection under various clinical scenarios, such as renal and/or liver impairment,
drug-drug interactions, and extrapolation from adult to children. By integrating gestational-dependent
physiological characteristics and drug-specific information, PBPK models can be used to predict PK during
pregnancy. Population pharmacokinetic (PopPK) modeling approach also could complement pregnancy clinical
studies by its ability to analyze sparse sampling data. In the past five years, PBPK and PopPK approaches for
pregnancy have made significant progress. We reviewed recent progress, challenges and potential solutions for
the application of PBPK, PopPK, and exposure-response analysis in clinical drug development for pregnancy.
