Effect of repeated administration of monomethyl-aminoantipyrine on the activities of gamma-glutamyltranspeptidase and microsomal drug metabolizing enzymes in rat liver.

The effects of consecutive administration of 4-monomethylaminoantipyrine, a metabolite of aminopyrine, on the gamma-glutamyltranspeptidase activities of liver, kidney, urine and serum were investigated in rats. On day 5 after repeated treatment, a pronounced increase of gamma-glutamyltranspeptidase activity was seen in the liver homogenate as well as in the hepatic microsomes. Furthermore, simultaneous administration of 4-monomethylaminoantipyrine with phenobarbital increased to the same degree as compared with the single administration of aminopyrine. However, no change in gamma-glutamyltranspeptidase activity was observed in kidney, urine, serum and hepatic cytosolic fractions. Under the same experimental condition, the contents of cytochrome P-450 and b5, NADPH cytochrome c reductase, the activities of aminopyrine N-demethylase and aniline hydroxylase were also enhanced.