Drug transport across the placenta, role of the ABC drug efflux transporters.
The placenta serves an important role both as a protective barrier as well as in normal fetal development. The ATP-binding cassette (ABC) proteins perform crucial functions in the distribution of nutrients and exchange of waste metabolites across the placenta. They also protect the developing fetus from xenobiotics to which the pregnant mother is exposed. Recent studies in P-glycoprotein (P-gp) deficient mdr1a and mdr1b (-/-) CF-1 mice have shown pronounced increases in fetal exposure to P-gp substrates due to increased transplacental penetration demonstrating the important protective role of P-gp to the developing fetus. The role of placental ABC transporter proteins in protecting the fetus against maternal exposure to drugs, toxins and other xenobiotics is discussed. Overall, the paucity of information available on the transplacental transfer of drugs emphasizes the need to further employ preclinical in vivo models for drug development in order to best predict fetal outcomes of drug administration to pregnant mothers.
Behravan
Javad
J
University of Toronto, Department of Pharmaceutical Sciences, 144 College Street, Toronto, Ontario, M5S 3M2, Canada.
Piquette-Miller
Micheline
M
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D015262:Xenobiotics / Q000378:metabolism / Q000493:pharmacokinetics*
D018528:ATP-Binding Cassette Transporters; D015262:Xenobiotics