[Role of monoxygenases in the metabolism of drugs in the human fetus and newborn infant].
Drug-metabolizing enzyme activities were assayed in human fetuses and neonates and compared with activities in adults. Among these enzymes, only UDP-glucuronosyltransferase exhibited a very low activity, whereas cytochromes P-450, epoxide hydrolase and glutathion S-transferase reached about 50% of adult values as soon as 15-20 weeks of gestational age. Multiple cytochromes P-450 were present in human adults: isoenzymes involved in the metabolism of exogenous substrates such as ethylmorphine, hexobarbital, aniline and diazepam, and endogenous substrates were present and active in the fetus, whereas isoenzyme(s) permitting the hydroxylation of polycyclic aromatic hydrocarbons exhibited a very low activity. A low number of transplacental inductions have been enzymatically studied; only correlations between the pharmacokinetics of a drug in neonates (full-term or premature) and drug intake of the mother during gestation were observed and showed that a treatment with barbiturates significantly increased drug elimination in neonates. Thus, in human fetus and neonate, drug-metabolizing enzymes are present and active, except UDP-glucuronosyltransferase which develops only after birth.
D000328:Adult; D000375:Aging; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000201:enzymology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008431:Maternal-Fetal Exchange; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011247:Pregnancy
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases
Rôle des mono-oxygénases dans le métabolisme des médicaments chez le foetus et le nouveau-né humain.