Abstract
On a single oral or subcutaneous administration of 5-methoxy-3-(2-methoxyphenyl)-1, 3, 4-oxadiazol-2(3H)-one, metoxadiazone (Elemic®), labeled with 14C at the benzene ring to male and female SD rats at a rate of 1mg/kg, 14C rapidly was excreted mainly into the urine. The cumulative urinary excretion of 14C amounted to 68-75% of the dose within 24hr and reached 80-90% within 7 days. 14C-Recoveries in the feces and expired air within 7 days were 7-18% and 0.1%, respectively. 14C-Levels in the liver, kidney and other tissues reached maximum 0.5-1hr after administration, which were 4.1, 2.0 and <1.0μg metoxadiazone equivalents per g tissue (ppm), respectively. The levels declined rapidly thereafter to below 1.0ppm within 24hr. 14C-Residue levels in the tissues on the 7th day were less than 0.1ppm. The 14C appeared to persist in the blood cell at very low concentrations. Nine metabolites were identified. Main metabolites in the urine were sulfates of N′-methoxycarbonyl-2-hydroxyphenylhydrazine, N′-carboxy-2-hydroxyphenylhydrazine and resorcinol. Unmetabolized metoxadiazone was not found either in the urine or feces. Main metabolic transformations of metoxadiazone were hydrolysis of the oxadiazolone ring, demethylation of the methoxyphenyl group and sulfuric acid conjugation.
