RT Journal Article SR Electronic T1 EFFECTS OF CHRONIC ADMINISTRATION OF BROMAZEPAM ON ITS BLOOD LEVEL PROFILE AND ON THE HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYMES IN THE RAT JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 235 OP 244 VO 3 IS 4 A1 HIDEO FUKAZAWA A1 HIROAKI IWASE A1 HIROKO ICHISHITA A1 TSUYOSHI TAKIZAWA A1 HIROTOSHI SHIMIZU YR 1975 UL http://dmd.aspetjournals.org/content/3/4/235.abstract AB After oral administration of bromazepam, 50 mg/kg/day for 14-28 days to rats, the rate of elimination of the unchanged drug from the blood increased by 20-40%, as determined from the half-lives of the blood decay curves during the first 4 hr after administration of an oral or intravenous test dose of bromazepam. During the chronic administration, the liver weight increased 30-40%, with concomitant enlargement of the liver. The hepatomegaly was associated with elevation of microsomal drug-metabolizing enzyme activities, including that responsible for the oxidation of bromazepam itself. Spectral characteristics of the isolated microsomes indicated that the manner by which bromazepam caused the elevation (induction) of the enzyme activities was of the "phenobarbital type" rather than the "methylcholanthrene type." Since certain steps of bromazepam metabolism take place in the liver, it appears reasonable to assume that the increase in the elimination rate found after chronic administration may depend upon the enhanced drug-metabolizing activities in the liver. The hepatomegaly and the associated elevation of enzyme activities returned to the normal states within 7 days after withdrawal of the drug. Neither the increase in the elimination rate nor the enzyme induction was observed with doses lower than 5 mg/kg. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics