抗アレルギー薬フマル酸エメダスチンのラット及びモルモットにおけるin Vitro代謝

抄録

In order to clarify the interspecies differences in the metabolism of emedastine difumarate (KG-2413), in vitro metabolism was studied with liver preparations of rats and guinea pigs. The activities of hydroxylase, N-oxidase and N-demethylase, of emedastine were evaluated with liver 9000×g supernatant and microsomes. As the results, the orders of activities were as follows ; 5-hydroxylase≨N-oxidase>6-hydroxylase>N-demethylase in rats, and N-oxidase»N-demethylase>6-hydroxylase>5-hydroxylase in guinea pigs. Emedastine N-oxide, little excreted into the urine of rats, was largely formed in vitro, so it was assumed that N-oxide reduction was important in vivo. The reductase activity of emedastine N-oxide was evaluated, and compared with N-oxidase activity of emedastine. In rats, the reductase activity was nearly equal to the N-oxidase activity, and relatively high even under aerobic conditions. On the other hand, in guinea pigs, the reductase activity was lower than the N-oxidase activity. It was considered that relative activities of the N-oxidation of tertiary amine in a 1, 4-diazepine ring of emedastine and the reduction of N-oxide once formed were one of the factors of interspecies differences of metabolism of emedastine in rats and guinea pigs.