alexa Fetal drug metabolism and its possible clinical implications.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Krauer B, Dayer P

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Abstract The ability of the human conceptus to metabolise xenobiotics during early gestation is now well established. Specific activities of liver enzymes have been demonstrated to exist in the late embryonic phase for numerous cytochrome P450 monooxygenases and many phase II enzymes such as glutathione-, N-acetyl-, sulpho- and uridine diphosphate-glucuronosyltransferase. As in the adult, fetal drug metabolism may function in a dual manner, either as a protective mechanism against chemical aggression when transforming active molecules into inactive ones, or as a toxifying system when transforming innocuous compounds into reactive metabolites. Recent advances in the understanding of enzyme variabilities at molecular and functional levels illustrate the necessity of studying these variations in the human fetus as well as in adults, since the combination of genetic, developmental and environmental factors seem to control fetal enzyme activities and ultimately determine the variability in individual susceptibility to chemicals in utero. Despite the scarcity of well documented cases of adverse fetal reactions resulting directly from metabolic toxicity, the clinical relevance of the potential role of biotransformation in generating fetal toxicity is a strong appeal to promote further studies dealing with the ontogeny of drug-metabolising capacity and its regulation. This article was published in Clin Pharmacokinet and referenced in Pharmaceutica Analytica Acta

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