Hydroxylation of three benzodiazepines in vitro.
Three structurally related benzodiazepines were studied as substrates for hydroxylation by liver microsomal enzymes of rats and mice. The Vmax was comparable for dechlorodesmethyldiazepam, desmethyldiazepam, and 2'-chlorodesmethyldiazepam in the two animal species. The apparent Km decreased from dechlorodesmethyldiazepam to 2'-chlorodesmethyldiazepam for liver microsomal enzymes from both animal species. The hydroxylation of desmethyldiazepam and 2'-chlorodesmethyldiazepam yielded two pharmacologically active metabolites, oxazepam and lorazepam, respectively.
D000818:Animals; D001711:Biotransformation; D003975:Diazepam / Q000031:analogs & derivatives*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D003708:Nordazepam / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats
D003708:Nordazepam; D003975:Diazepam