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Metabolic fate of tolazamide in man and in the rat

Authors :
Richard C. Thomas
David J. Duchamp
George J. Ikeda
Ray W. Judy
Source :
Journal of Medicinal Chemistry. 21:725-732
Publication Year :
1978
Publisher :
American Chemical Society (ACS), 1978.

Abstract

The metabolic fate of tolazamide, 1-(hexahydroazepin-1-yl)-3-p-tolylsulfonylurea (1), was studied in man and in the rat using tritium-labeled 1. The metabolites were isolated in crystalline form from urine for structure determination. The crystal structure and final molecular structure of one of these, 1-(4-hydroxyhexahydroazepin-1-yl)-3-p-tolylsulfonylurea (5), were determined using single-crystal X-ray techniques. Following oral administration of tritiated tolazamide to male humans, 85% of the radioactivity was excreted in urine during a 5-day period. In addition to being excreted in urine unchanged, tolazamide was metabolized to 1-(hexahydroazepin-1-yl)-3-p-(carboxyphenyl)sulfonylurea (2), p-toluenesulfonamide (3), 1-(hexahydroazepin-1-yl)-3-p-(hydroxymethylphenyl)sulfonylurea (4), 1-(4-hydroxyhexahydroazepin-1-yl)-3-p-tolylsulfonylurea (5) and a labile, unidentified metabolite 6 by man. The relative amounts of these materials excreted in 0-24-h urine collections from eight subjects averaged 7, 17, 26, 10, 25, and 15% for 1-6, respectively. In the female rat, 79% of an orally administered dose of tritiated tolazamide was excreted in urine during a 5-day period as 1-4. The relative amounts of these materials excreted during the 24-h period following administration of tolazamide were 10, 5, 5, and 80% for 1-4, respectively.

Details

ISSN :
15204804 and 00222623
Volume :
21
Database :
OpenAIRE
Journal :
Journal of Medicinal Chemistry
Accession number :
edsair.doi.dedup.....e9eb25f54838e65a6bc3462c97862cea
Full Text :
https://doi.org/10.1021/jm00206a002