Active transport across the human placenta: impact on drug efficacy and toxicity.
The human placenta expresses a large number of transport proteins. The ATP-binding cassette (ABC) family of active efflux pumps, predominantly localised to the maternal-facing syncytial membrane of placental microvilli, comprise the major placental drug efflux transporters. A variety of other transporters are also expressed in the placenta that can facilitate xenobiotic transfer in both the maternal and fetal directions. Many drugs administered in pregnancy are ABC transporter substrates, and many are either teratogenic or fetotoxic. The in vitro, in vivo and clinical evidence reviewed in this article argues that active efflux of drugs by placental transporters helps to maintain its barrier function, reducing the incidence of adverse fetal effects. ABC transporter polymorphisms may explain the wide variability observed in fetal drug concentrations, incidence of teratogenesis or drug failure in pregnancies exposed to therapeutic agents. Although our understanding of the molecular mechanics and dynamics of placental drug transfer is advancing, much work is needed to fully appreciate the significance of placental drug transporters in the face of increasing drug administration in pregnancy.
Evseenko
Denis
D
University of Auckland, Liggins Institute, Faculty of Medical and Health Science, Auckland, New Zealand.
Paxton
James W
JW
Keelan
Jeffrey A
JA
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy
D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations