In vivo metabolism and anti-inflammatory activity of benzydamine hydrochloride in rats treated with carrageenin.

Abstract

The present study was made to evaluate the anti-inflammatory action of benzydamine hydrochloride (BZY-HCl) in relation to its metabolism. In rats given BZY·HCl orally, unconjugated metabolites (consisting mainly of benzydamine N-oxide) were predominantly excreted in urine, but conjugated metabolites (mainly consisting of glucuronides) were predominant in the bile. Moreover, it appeared that enterohepatic circulation occurred during the metabolism of BZY·HCl, then the levels of conjugated metabolites decreased greatly with time. In rat blood, unconjugated BZY and benzydamine N-oxide (BZY-NO) were predominant, whereas in the blood of rabbits, a conjugated metabolite (G-1) was predominant. However, in rats treated with carrageenin as an inflammation model, the levels of BZY-NO apparently increased in the blood and inflamed paw. The anti-edematous and analgesic potencies of BZY-NO hydrogen maleate (BZY-NO maleate) were determined simultaneously with the anti-inflammatory action. In the case of intravenous injection, BZY-NO maleate did not show anti-edematous or analgesic action, whereas in the case of oral administration, it showed anti-edematous action amounting to two-thirds of that of the parent drug BZY·HCl, and analgesic action similar to that of BZY·HCl. In addition, it was confirmed that BZY-NO maleate was well absorbed in the body by oral administration, and was reduced to the parent drug BZY. It is suggested that the effect of oral administration of BZY-NO maleate was due to BZY formed by the reduction of BZY-NO in the rat body.