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Absorption, distribution and metabolic fate of 2,3-dihydro-9H-isoxazolo-[3,2-b]quinazolin-9-one (W2429).

After oral administration to rats, mice, beagle dogs and human volunteers, 2,3-dihydro-9H-isoxazolo [3,2-b]-quinazolin-9-one (W 2429) is readily absorbed. The initial half-lives for the elimination from the circulation of these four species are about 240, 20, 40 and 120 min, respectively. Studies in the rat, using 9-14C-W-2429 and 3a-14C-W-2429, showed that more than half of the radioactivity is excreted in the urine. The major urinary metabolite in the rat and dog is a conjugated form of W-2429. Metabolic cleavage of the pyrimidone ring of W-2429 yields 3-(o-carboxyphenylimino)isoxazolidine, which in turn is converted to anthranilic and malonic acids. Anthranilic acid is acetylated and hydroxylated, and these products are excreted partly in the form of their glycine and glucuronic acid conjugates. The isoxazole ring of W-2429 is also dehydrogenated during metabolism to yield 9H-isoxanzolo-[3,2-b]quinazolin-9-one.