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妊娠期药物治疗;ABC 和 SLC 转运蛋白对药物跨胎盘转运和胎儿药物暴露的影响。

Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure.

机构信息

Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Czech Republic.

出版信息

J Drug Target. 2012 Nov;20(9):736-63. doi: 10.3109/1061186X.2012.716847. Epub 2012 Sep 20.

DOI:10.3109/1061186X.2012.716847
PMID:22994411
Abstract

Pharmacotherapy during pregnancy is often inevitable for medical treatment of the mother, the fetus or both. The knowledge of drug transport across placenta is, therefore, an important topic to bear in mind when deciding treatment in pregnant women. Several drug transporters of the ABC and SLC families have been discovered in the placenta, such as P-glycoprotein, breast cancer resistance protein, or organic anion/cation transporters. It is thus evident that the passage of drugs across the placenta can no longer be predicted simply on the basis of their physical-chemical properties. Functional expression of placental drug transporters in the trophoblast and the possibility of drug-drug interactions must be considered to optimize pharmacotherapy during pregnancy. In this review we summarize current knowledge on the expression and function of ABC and SLC transporters in the trophoblast. Furthermore, we put this data into context with medical conditions that require maternal and/or fetal treatment during pregnancy, such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy. Proper understanding of the role of placental transporters should be of great interest not only to clinicians but also to pharmaceutical industry for future drug design and development to control the degree of fetal exposure.

摘要

在妊娠期间,药物治疗通常是不可避免的,无论是为了治疗母亲、胎儿还是两者。因此,在为孕妇决定治疗方案时,了解药物在胎盘内的转运是一个重要的考虑因素。已经在胎盘内发现了 ABC 和 SLC 家族的几种药物转运体,如 P-糖蛋白、乳腺癌耐药蛋白或有机阴离子/阳离子转运体。因此,药物通过胎盘的传递不能再仅仅基于其物理化学性质来预测。必须考虑胎盘药物转运体在滋养层中的功能表达和药物相互作用的可能性,以优化妊娠期间的药物治疗。在这篇综述中,我们总结了目前关于 ABC 和 SLC 转运体在滋养层中的表达和功能的知识。此外,我们将这些数据与需要在妊娠期间对母亲和/或胎儿进行治疗的医疗状况联系起来,例如妊娠期糖尿病、HIV 感染、胎儿心律失常和癫痫。正确理解胎盘转运体的作用不仅对临床医生而且对制药行业在未来的药物设计和开发中控制胎儿暴露程度都具有重要意义。

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