[Drug interaction between imipramine hydrochloride and benzodiazepines when administered orally for 15 days]

The effects of daily oral administration of imipramine (IM) hydrochloride (50 mg/kg) and/or oxazepam (OZ, 20 mg/kg) or diazepam (DZ, 5 mg/kg) in a 1% aqueous solution of carboxymethylcellulose sodium salt (CMC) on the activities of drug metabolizing enzyme systems and steady state plasma levels of IM, desmethylimipramine (DIM), DZ, desmethyl-diazepam (DDZ) and OZ were investigated in rats during a 15-day period. In addition, the effect of a single intravenous administration of IM hydrochloride (5 mg/kg), DZ (0.5 mg/kg) and OZ (2 mg/kg) on plasma concentration-time profiles of IM, DIM, DZ, DDZ and OZ was investigated in rats given the same drug treatments by the oral route for 14 days. The group treated with IM hydrochloride plus OZ group showed a great increase in drug-metabolizing enzyme activities, but the difference for the group given IM hydrochloride was not statistically significant. The steady-state plasma levels of DZ after oral administration for 15 days suggested that the group given IM hydrochloride plus DZ did show accumulated DZ. In terms of the area under the concentration-time curve of IM, DZ and OZ after intravenous administration of IM hydrochloride, DZ and OZ, there were significant differences between each of the mono-treatment groups and the IM hydrochloride plus DZ or OZ treatment groups. In conclusion, we have found that the drug interaction for IM hydrochloride by OZ is markedly lower than that by DZ.