Efflux transporters in drug disposition during pregnancy.

Abstract

Evidence-based dose selection of drugs in pregnant women has been lacking because of challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from nonpregnant women. During pregnancy, drug transporters play an important role in drug disposition along with known gestational age-dependent changes in physiology and drug-metabolizing enzymes. In this review, as Dr Qingcheng Mao's former and current laboratory members, we summarize the collective contributions of Dr Mao, who lost his life to cancer, focusing on the role of drug transporters in drug disposition during pregnancy. Dr Mao and his team initiated their research by characterizing the structure of breast cancer resistance protein (ATP-binding cassette G2). Subsequently, they have made significant contributions to the understanding of the role of breast cancer resistance protein and other transporters, particularly P-glycoprotein (ATP-binding cassette B1), in the exposure of pregnant women and their fetuses to various drugs, including nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol, and their metabolites. This review also highlights the gestation- and pregnancy-dependent transporter expression at the blood-brain and blood-placenta barriers in mice. SIGNIFICANCE STATEMENT: Dr Qingcheng Mao and his team have made significant contributions to the investigation of the role of efflux transporters, especially P-glycoprotein and breast cancer resistance protein, in maternal-fetal exposure to many xenobiotics: nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol, and their metabolites. Studies of individual compounds and the expression of transporters during gestation and pregnancy have improved the understanding of maternal-fetal pharmacokinetics.