The disposition of 3-methyl-2,3-dihydro-9H-isoxazolo[3,2-b]-quinazolin-9-one (W-2451)

3-Methyl-2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one was readily absorbed, metabolized and eliminated in rat, dog, monkey and man. The radioactivity elimination after i.v. or p.o. administration of W-2451-14C in rats was biphasic with corresponding half-lives of 1.8 and 8.7 hours. Plasma half-lives of W-2451 in the dog, rhesus monkey and man were 1.4, 1.2 and 3.2 hours, respectively. In the rat, excretion via the urine was predominant, no significant accumulation in tissue occurred. The only major metabolite found in rat and dog urine, rat plasma and in the rat liver 9000 g supernatant fraction was the 3-hydroxy derivative of the drug. The unsaturated compound with the double bond in the 2,3-position and Other hydroxylated metabolites were also present. Very little free or conjugated anthranilic acid and 3-(o-carboxy-phenylimino)-4-methylisoxazolidine were found.