Active and passive transport of drugs in the human placenta.
The human placenta, characterized by the processes of passive transport and facilitated diffusion, contains numerous active transport proteins, usually located in the microvilli of the syncytiotrophoblast or in the endothelium of the capillaries of the villi. These proteins use either the energy from ATP hydrolysis or other mechanisms resulting, among others, from the formation of the maternofetal ion gradient, which facilitates the transfer of various endogenous substances or xenobiotics across the body membranes. The proteins either trigger the efflux of these substances from the fetal tissues via the placenta into the maternal bloodstream, or conversely they accumulate them in the fetal tissues. Both the placenta and the fetus are equipped with independent systems of enzymes of 1st and 2nd phase of substrate metabolism, such as CYP450, glucuronyltransferase or sulphatase. An active therapy with a wide range of drugs, often at high toxicity levels, either shortly before or during pregnancy, has naturally posed a question concerning the degree of impermeability of the placental barrier and how effectively it can be crossed, including any possible negative embryotoxic or teratogenic consequences. Such hazards seem to be quite real, as many drugs are substrates for ABC transporters. Also the placenta itself, including its structure, is subject to vast transformations during pregnancy which may be observed as the thinning of the barrier separating the maternal blood from the fetal one, from 20-30 microm in the first trimester of gestation down to 2-4 microm in the third trimester of gestation.
Włoch
Stanisław
S
Department of Obstetrics and Gynaecology, Medical University of Silesia, Katowice, Poland.
Pałasz
Artur
A
Kamiński
Marcin
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001692:Biological Transport; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology*; D008871:Microvilli / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D015262:Xenobiotics / Q000493:pharmacokinetics
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System