Metabolism of an antiallergic Agent, 1-(2-Ethoxyethyl)-2-(hexahydro-4-methyl-1H-1, 4-diazepin-1-yl)-1H-benzimidazole Difumarate (KG-2413), in Rats and Guinea Pigs

Abstract

The metabolism of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1, 4-diazepin-1-yl)-1H-benzimidazole difumarate (KG-2413), was studied in rats and guinea pigs after oral administration of the ¹⁴C labelled compound.
KG-2413 and its metabolites in the urine, bile, plasma and liver of rats were quantified. The major metabolites of KG-2413 in rats were 5-hydroxylated compound (M 5 b), 6-hydroxylated compound (M 5 a) and their conjugated metabolites. Tracer concentration of the unchanged drug was found, so it was assumed that KG-2413 was rapidly metabolized in rats.
The urinary metabolites in guinea pigs were also quantified. The major metabolite was N-oxide compound (M9), and M 5 a and M 5 b were present mostly as conjugated metabolites, but the amounts of them were about one sixth of M9. The urinary excretion of the unchanged drug in guinea pigs was higher than that in rats.
There were remarkable interspecies differences in the urinary excretion of the metabolites after oral administration of KG-2413.