Drug biotransformation in the placenta

Abstract

In comparison with the heavily investigated hepatic drug metabolic process, placental drug metabolism remains virtually unexplored. Much of the available data is of a preliminary, exploratory nature and much is also conflicting. It has become evident, however, that in comparison with the liver, the placenta possesses a very limited capacity to biotransform foreign organic molecules. The limitation appears to apply both to the quantity of enzymes that have been detected, as well as to the number and variety of actual enzymes present. Nevertheless, certain metabolic pathways for xenobiotic biotransformation do exist in placental tissues and, in some cases, these may be quite efficient. Nearly all of the common ‘classical’ drug metabolic pathways have been detected in placental tissues; no unusual metabolic pathways have been described. A concern which has arisen in recent years pertains to the relative activities of bioactivating vs inactivating placental enzymes. Results indicate that in cases of exposure to methylcholanthrene-type inducing agents (e.g. via cigarette smoking) the ratio of bioactivation to inactivation may be sufficiently high to be of major concern. Thus, recent studies have focused on the capacity of placental tissues to convert promutagenic and procarcinogenic organic chemicals into their active forms.