title: Metabolism of diazepam in vitro by human liver. Independent variability of N-demethylation and C3-hydroxylation.
abstract: The interindividual variability of diazepam metabolism was studied using human livers. The formation of N-desmethyldiazepam (NDZ) and 3-hydroxydiazepam (temazepam, TMZ), was monitored by gas chromatography. In 10 livers, Km values for NDZ and TMZ formation varied independently from each other, each by a factor of 4, from 100 to 400 microM. This variability is consistent with the presence of at least two different cytochrome P-450 species controlling formation of these metabolites. In the same livers, Vmax for NDZ and TMZ production varied 6-fold and 15-fold, respectively.
mesh_terms: D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003975:Diazepam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D003708:Nordazepam / Q000378:metabolism*; D010084:Oxidation-Reduction; D013693:Temazepam / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D003708:Nordazepam; D003577:Cytochrome P-450 Enzyme System; D013693:Temazepam; D003975:Diazepam