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.