Absorption, distribution, and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one in rats, dogs, and humans

✍ Scribed by Jerome Edelson; J. F. Douglas; B. J. Ludwig; E. B. Schuster; S. Shahinian

• Publisher: John Wiley and Sons
• Year: 1975
• Tongue: English
• Weight: 581 KB
• Volume: 64
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600640812

✦ Synopsis

The absorption and metabolic fate of 7-chloro-3,3adihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)( 1,3)-benzoxazin-9-one (I) was studied in rats, dogs, and humans. Orally administered I was readily absorbed by all species. In the rat, orally administered I was converted to its metabolite, 5-chlorosalicylic acid, by the intestinal wall. The half-lives of blood radioactivity, after the oral administration of I-9-14C, were about 18 and 12 hr in the rat and beagle hound, respectively. In human subjects, no intact I was detected in the bloodstream; however, the clearance of the metabolite, 5-chlorosalicylic acid, had a half-life of about 33 hr. Cleavage of the oxazine ring of I generated 5-chlorosalicylic acid, which was excreted both in the free form and conjugated with glycine and glucuronic acid. The isoxazole moiety was converted to b-hydroxybutyric acid and its metabolites carbon dioxide and fumaric, citric, a-ketoglutaric, succinic, and malic acids. Binding of I to plasma proteins was extensive but was less than that of 5-chlorosalicylic acid.

Keyphrases 7-Chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one-absorption, distribution, and metabolic fate, rats, dogs, and humans 0 5-Chlorosalicylic acid-identified as major metabolite of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(l,3)-benzoxazin-9-one in rats, dogs, and humans GLC-analysis, 7-chloro-3,3a-dihydro-2-methyl-2H,9Hisoxazolo-( 3,2b) (1,3) -benzoxazin -9-one in plasma