Placental Drug Disposition and Its Clinical Implications

Shu-Feng      Zhou; Naomi      Weier; Shu-Ming      He; Xiao-Tian      Li; Lin-Lin      Wang

Abstract

The placenta is a unique organ that is essential to a healthy and normal pregnancy. A number of phase I and II metabolizing enzymes are expressed at moderate levels in the placenta, and have been proven to have the ability to metabolize certain xenobiotics. Depending on the substrate, this metabolic action may have significant clinical implications on how it affects the fetus. A wide variety of transporters including P-glycoprotein, breast cancer resistance protein, and multidrug resistance associated proteins have also been discovered in the placenta, and while most are found to have mainly physiological substrates, there are a number of xenobiotics which are also able to gain access to the fetus through transport across the placenta. Depending on the xenobiotics and its intended action, drug transport across the placenta may be desired, acceptable or undesirable. Medications administered to the mother but designed to work on the fetus are now being used increasingly, and demonstrates an important clinical implication in which drug transport across the placenta is desirable. However, medications designed to treat the mother but are also able to cross the placenta carry potential risks to damage the developing fetus, and it is therefore essential that the effects of different drugs on the fetus are known before they are administered during pregnancy. There is still much unknown about drug transport and drug metabolism in the placenta, and it is vital that in the future further research is done to discover the clinical implications of these activities in the placenta. This research is often complicated by the fact that it is unethical to run studies in pregnant women, and so research is often carried out in pregnant animals. These results are not always accurate, however, as the humans placental structure is different from the placenta in other animals. Drug metabolism and drug transport across the placenta should continue to be researched, and guidelines need to be developed to ensure that any medications used during pregnancy are safe to both the mother and the fetus, and that successful treatment of the medical condition is carried out.

Keywords: Placenta, drug metabolism, drug transporter, cytochrome P450, P-glycoprotein