Biotransformations of drugs and foreign chemicals in the human fetal-placental unit.

Several communications pertaining to research on human fetal drug biotransformation have appeared in the literature in the past 3 to 4 years (Aranda et al. 1979; Cresteil et al. 1982; Pacifici et al. 1981; Pacifici and Rane 1982, 1983; Schroeter and Amon 1983). In general, research in this area has produced no major recent surprises, but it has confirmed, extended, and supported the earliest findings through those of the mid-1970s and has served to expand our understanding of these important systems. The important aspects of our current knowledge may be summarized very briefly as follows: Each of the major drug metabolic reactions (oxidations, reductions, hydrolyses, and conjugations) can be catalyzed at generally low rates by enzymes present in human fetal and placental tissues. Reaction rates appear, in general, to increase with advancing gestational age. Placental xenobiotic-biotransforming monooxygenases display a high sensitivity to the effects of MC-type (methylcholanthrene) but not PB-type (phenobarbital) inducing agents during the later stages of gestation. Responsivity is minimal during early gestation. Monooxygenases in other fetal tissues (liver, adrenal gland, etc.) appear to respond minimally to inducing agents, at least during the earlier stages of gestation. Glucuronyl transferase activities appear to be very low in all fetal and placental tissues. Epoxide hydrolase, glutathione S-transferase, and sulfotransferase (and perhaps others) activities can be relatively high in prenatal primate hepatic tissues but, at present, are difficult to predict. Some of these may respond to environmental inducers in situ, but solid evidence for this is still lacking.(ABSTRACT TRUNCATED AT 250 WORDS)