Dizepam metabolism in human foetal and adult liver.
Diazepam was metabolized by human foetal liver microsomes to N-desmethyldiazepam and N-methyloxazepam as early as the 13th week of gestation. The metabolic activity was lower than that of microsomes from adult human liver. Diazepam was shown mainly to be hydroxylated to N-methyloxazepam at substrate concentrations higher than 0.1 mM. Diazepam levels above 1.0 mM were inhibitory to the overall metabolic reaction. SKF 525-A inhibited diazepam metabolism by foetal liver microsomes at a concentration of 0.1 mM. The addition of diazepam to foetal and adult human liver microsomes resulted in a type II spectral change. Its inhibition by carbon monoxide indicated that biotransformation of diazepam was performed by the cytochrome P-450-linked mono-oxygenase system.
D000375:Aging; D002248:Carbon Monoxide / Q000494:pharmacology; D003640:Dealkylation; D003864:Depression, Chemical; D003975:Diazepam / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000196:embryology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011335:Proadifen / Q000494:pharmacology; D013053:Spectrophotometry; D013997:Time Factors
D002248:Carbon Monoxide; D011335:Proadifen; D003975:Diazepam