Effects of combined administration of diazepam and imipramine hydrochloride in rats

Abstract

The effects of daily oral administration of imipramine hydrochloride (5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz-[b,f]azepine monohydrochloride; 50 mg/kg) and/or diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one ; 5 mg/kg) in a 1% aqueous solution of carboxymethylcellulose sodium salt (CMC) on the body weight, organ weights, and activities of various enzymes, including drug metabolizing enzyme systems were investigated in rats during a 15-day period. The plasma concentrations of imipramine and desipramine were also determined. In addition, the effect of a single intravenous administration of imipramine hydrochloride (5 mg/kg) on the plasma concentration-time profiles of imipramine and desipramine was investigated in rats given the same drug treatments. The plasma concentration-time profiles of imipramine and desipramine were analyzed pharmacokinetically. The rats treated with imipramine hydrochloride showed a greater inhibition of body weight gain than those treated with diazepam, and those treated with imipramine hydrochloride and diazepam simultaneously showed a body weight gain similar to those treated with imipramine hydrochloride alone. No significant differences in organ weight (per 100 g of body weight) were found. The imipramine hydrochloride plus diazepam treatment group showed a greater increase in drug-metabolizing enzyme activities than the imipramine hydrochloride treatment group, but the difference was not statistically significant. However, the plasma levels of imipramine and desipramine after oral administration for 15 d suggested that the imipramine hydrochloride plus diazepam treatment group did not show increased imipramine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)