M, in single and multiple doses on hypatic microsomal aminopyrine n-demethylase and aniline hydroxylase activities in the rat: comparison with the effects of skf 525-A

ABSTRACT

The effects of diclofenac sodium administration, in single and repeated doses, on hepatic microsomal activities of aminopyrine N- demethylase and aniline hydroxylase were evaluated in rats. Two groups of rats treated with SKF 525-A, were used to demonstrate the inhibition and induction of these enzymes. In rats treated with a single dose [50 mg/kg] of SKF 525-A, aminopyrine N-demethylase and aniline hydroxylase activities were significantly decreased, compared with control values. Under similar experimental conditions, diclofenac sodium administration, in a dose of 2.5 mg/kg, did not affect the activities of these enzymes. With repeated daily administration of diclofenac sodium for 15 days, a dose-dependent induction of the microsomal enzymes was evident. With a dose of 2.5 mg/kg/day, a significant increase in the activities of the two enzymes was observed. The extent of this induction was greater than that caused by repeated doses [50 mg/kg/day] of SKF 525-A. Rats treated with a smaller dose of the drug [1.25 mg/kg/day], did not show a similar response. In conclusion, repeated administration of daily doses of diclofenac sodium may induce hepatic microsomal drug metabolism depending on the dose used