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.