The influence of cyclobarbital and diazepam on drug metabolism in vitro and their binding to cytochrome P-450.
Cyclobarbital inhibited diazepam metabolism by rat liver supernatant only at concentrations of 1 mM. Ethylmorphine N-demethylation is strongly inhibited by diazepam in a non-competitive manner whereas cyclobarbital shows a competitive inhibition type. Both cyclobarbital and oxazepam are weak inhibitors. Hexobarbital- evokes typical type I spectral changes with rat liver microsomes whereas cyclobarbital and diazepam-induced spectral changes are similar to type II or inverse type I. Barbital evoked the same type of spectral changes as diazepam and cyclobarbital. With the usual concentration in vivo the metabolism of diazepam and other drugs can scarcely be influenced by cyclobarbital.
D000818:Animals; D001462:Barbital / Q000378:metabolism; D001463:Barbiturates / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology*; D005036:Ethylmorphine / Q000378:metabolism*; D006591:Hexobarbital / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009022:Morphine Derivatives / Q000378:metabolism*; D010076:Oxazepam / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001463:Barbiturates; D009022:Morphine Derivatives; D001462:Barbital; D010076:Oxazepam; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D003975:Diazepam; D005036:Ethylmorphine