Toward Greater Insights on Applications of Modeling and Simulation in Pregnancy
Toward Greater Insights on Applications of Modeling and Simulation in Pregnancy
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更深入地了解建模和仿真在怀孕中的应用
DOI：
10.2174/1389200221666200907143941
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发表时间：
2020
影响因子：
2.3
通讯作者：
Dongyang Liu
中科院分区：
文献类型：
--
作者：
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;Dongyang Liu
孕妇通常被排除在常规临床试验之外。因此，该人群中大多数药物的适当给药方案未知，这可能导致该未研究人群出现非预期安全性问题或疗效不足。通过对妊娠进行临床研究来确立证据仍然是一个挑战。近几十年来，基于生理学的药代动力学（PBPK）建模已被证明可用于支持各种临床情况下的剂量选择，如肾和/或肝损伤、药物-药物相互作用以及从成人外推至儿童。通过整合妊娠依赖性、生理特征和药物特异性信息，PBPK模型可用于预测妊娠期间的PK。群体药代动力学（PopPK）建模方法也可以通过其分析稀疏采样数据的能力来补充妊娠临床研究。在过去的五年里，PBPK和PopPK方法在妊娠方面取得了重大进展。本文综述了PBPK、PopPK和药物效应分析在妊娠药物临床开发中的应用进展、面临的挑战和可能的解决方案。
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.