Drug-metabolizing activity of the human placenta

The drug-metabolizing activity of a 9000 × g supernatant fraction prepared from human placentae obtained immediately after birth was investigated. For comparative purposes a similar rat liver microsomal preparation was used. The metabolism of pentobarbital by oxidation, and of amphetamine by deamination or hydroxylation, proceeded at similar rates in the two tissues. The rate of metabolism of meperidine in the human placental preparation was about two-thirds of that found with the rat liver enzyme. The rate of metabolism of aminopyrine, as determined by measuring the formation of 4-aminoantipyrine or the production of formaldyhyde, was insignificant in the placental preparation, but the metabolism of 4-aminoantipyrine occurred much more rapidly in this tissue than in rat liver. The nitroreductase activity of the human placenta was low; a sixfold activation was achieved by adding a source of glucose 6-phosphate dehydrogenase but the activity was still only one-third of that found in rat liver. The cofactor requirements for the drug-metabolizing enzymes studied were found to be similar in the two tissues. The significance of these findings with respect to the effects of drugs on the mother and the fetus is discussed.