Enzyme induction with high doses of rifampicin in Wistar rats.

Hepatic microsomal enzyme activities were determined in female Wistar rats after 1 and 8 days of oral administration of high doses of rifampicin (RFP) (400 mg/kg/day). After 8 days, the level of cytochrome P-450 doubled and the activities of NADPH-cytochrome c reductase and benzphetamine N-demethylase were significantly increased. The observed changes in enzymic activities are consistent with the possibility that RFP induces a special form of cytochrome P-450, responsible for the metabolism of the antibiotic (demethylation and reduction of rifampicin quinone). Considering the role of the endoplasmic reticulum in lipid metabolism, the inducing activity of RFP might also contribute to the observed accumulation of lipids in the liver.