Fetal Drug Metabolism and Its Possible Clinical Implications

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.

The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

“…As pregnancy progresses, fetal metabolic capacity increases but at birth decreases dramatically [ 250 , 314 , 396 ]. In addition, methadone has been identified in amniotic fluid, suggesting oral and cloacal uptake, although such exposure is presumably minimal compared to that received across the placenta [ 128 , 211 , 212 , 326 ].…”

The Impacts of Cord Blood Cotinine and Glutathione-S-Transferase Gene Polymorphisms on Birth Outcome

“…Fetal enzyme activity may differ from that of adults, and enzyme expression varies during various pregnancy periods. 33 The GST enzyme is one of the important detoxification enzymes for substances passing through the placenta. It catalyzes the conjugation of glutathione to toxic compounds, resulting in more watersoluble and less biologically active products that are easily excreted.…”

Pharmacokinetic Optimisation of General Anaesthesia in Pregnancy

“…The fetus and neonate are capable of metabolising drugs (Krauer & Dayer 1991). The fetus is able to transfer drugs back to the mother but the neonate must rely on its own elimination pathways.…”