Maternal-Fetal Pharmacology of Drugs: A Review of Current Status of the Application of Physiologically Based Pharmacokinetic Models

Frontiers in Pediatrics

Steve Caritis¹  Raman Venkataramanan²  Prerna Dodeja³  Nupur Chaphekar³  Imam H. Shaik³ 

[1] Department of Obstetrics, Gynecology and Reproductive Sciences, Magee Women's Hospital of UPMC, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States;Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States;Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States;

关键词: maternal;    fetal;    pharmacology;    pregnancy;    PBPK;   

DOI  :  10.3389/fped.2021.733823

来源: DOAJ

【 摘 要 】

Pregnancy and the postpartum period are associated with several physiological changes that can alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. For certain drugs, dosing changes may be required during pregnancy and postpartum to achieve drug exposures comparable to what is observed in non-pregnant subjects. There is very limited data on fetal exposure of drugs during pregnancy, and neonatal exposure through transfer of drugs via human milk during breastfeeding. Very few systematic clinical pharmacology studies have been conducted in pregnant and postpartum women due to ethical issues, concern for the fetus safety as well as potential legal ramifications. Over the past several years, there has been an increase in the application of modeling and simulation approaches such as population PK (PopPK) and physiologically based PK (PBPK) modeling to provide guidance on drug dosing in those special patient populations. Population PK models rely on measured PK data, whereas physiologically based PK models incorporate physiological, preclinical, and clinical data into the model to predict drug exposure during pregnancy. These modeling strategies offer a promising approach to identify the drugs with PK changes during pregnancy to guide dose optimization in pregnancy, when there is lack of clinical data. PBPK modeling is also utilized to predict the fetal exposure of drugs and drug transfer via human milk following maternal exposure. This review focuses on the current status of the application of PBPK modeling to predict maternal and fetal exposure of drugs and thereby guide drug therapy during pregnancy.

【 授权许可】

Unknown