Effect of chronic oral delorazepam on in vitro and in vivo hepatic drug-metabolizing enzyme activities in the rat.
In vivo (delorazepam clearance) and in vitro (monooxygenase activity markers) alterations in drug metabolism and the extent of enzyme induction of the hepatic cytochrome P-450 system were evaluated after oral administration of delorazepam (2.5, 25 and 150 mg/kg) for two weeks to male Sprague-Dawley rats. This benzodiazepine had no significant effect on drug metabolizing enzymes, except for slight enhancement of in vitro aniline p-hydroxylase activity which occurred at doses approximately 100 times those used clinically (0.5-2 mg). Under the likely conditions of exposure to delorazepam in human therapy therefore, such alteration in liver enzymes would be unlikely to have clinical relevance.
Conti
I
I
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Tridico
R V
RV
Caccia
S
S
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003975:Diazepam / Q000031:analogs & derivatives*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D003708:Nordazepam / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D003708:Nordazepam; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C013434:chlordesmethyldiazepam; D003975:Diazepam; D010634:Phenobarbital