Gong Christine, Bertagnolli Lynn N, Boulton David W, Coppola Paola
School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
AstraZeneca LP, Biopharmaceuticals R&D, Clinical Pharmacology & Safety Sciences, Clinical Pharmacology & Quantitative Pharmacology, Gaithersburg, MD 20878, USA.
Pharmaceutics. 2023 Nov 15;15(11):2624. doi: 10.3390/pharmaceutics15112624.
The purpose of this literature review is to comprehensively summarize changes in the expression of phase II drug-metabolizing enzymes and drug transporters in both the pregnant woman and the placenta. Using PubMed, a systematic search was conducted to identify literature relevant to drug metabolism and transport in pregnancy. PubMed was searched with pre-specified terms during the period of 26 May 2023 to 10 July 2023. The final dataset of 142 manuscripts was evaluated for evidence regarding the effect of gestational age and hormonal regulation on the expression of phase II enzymes ( = 16) and drug transporters ( = 38) in the pregnant woman and in the placenta. This comprehensive review exposes gaps in current knowledge of phase II enzyme and drug transporter localization, expression, and regulation during pregnancy, which emphasizes the need for further research. Moreover, the information collected in this review regarding phase II drug-metabolizing enzyme and drug transporter changes will aid in optimizing pregnancy physiologically based pharmacokinetic (PBPK) models to inform dose selection in the pregnant population.
本综述的目的是全面总结孕妇和胎盘中II期药物代谢酶和药物转运体表达的变化。利用PubMed进行了系统检索,以识别与孕期药物代谢和转运相关的文献。在2023年5月26日至2023年7月10日期间,使用预先指定的术语对PubMed进行了检索。对最终的142篇手稿数据集进行了评估,以获取有关孕周和激素调节对孕妇和胎盘中II期酶(n = 16)和药物转运体(n = 38)表达影响的证据。这一全面综述揭示了目前关于孕期II期酶和药物转运体定位、表达和调节知识的空白,强调了进一步研究的必要性。此外,本综述收集的关于II期药物代谢酶和药物转运体变化的信息将有助于优化基于生理的药代动力学(PBPK)模型,为孕妇群体的剂量选择提供依据。