The absorption. distribution, and metabolic fate of seclazone was studied in the rat, dog, and rhesus monkey. Seclazone is readily absorbed by all species. The half-life of blood radioactivity following oral administration of seclazone-9J4C was 10.8.5, and 6 hr. in the rat, beagle hound, and rhesus monkey, respectively. Studies in the rat, using seclazone-9J4C, indicated that about one-half of the radioactivity was excreted in the urine within 20 hr. Significant amounts of 14C were also found in the carcass, liver, and GI tract. Only trace amounts of unchanged drug were voided. Seclazone undergoes metabolic cleavage of the oxazine ring, yielding S-chlorosalicylic acid which is excreted in the free form and as conjugates with glucuronic acid and glycine. Similar studies using seclazone-2-I4C showed that the carbon chain of the isoxamline ring is cleaved t o malonic acid and carbon dioxide.
Keyphrsses 0 Seclazone, radiolabeled-absorption, distribution, metabolism in rats, dogs, rhesus monkeys 0 7-Chloro-3,3a-dihydro-2H,9H-isoxazolo(3,2-b)(l,3)benzoxazin-9-one, radiolabeled -absorption, distribution, metabolism in rats, dogs, rhesus monkeys 0 5-Chlorosalicylic acid-major metabolite of seclazone