title: Metabolic fate of tolazamide in man and in the rat.
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.
mesh_terms: D000818:Animals; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D002854:Chromatography, Paper; D002855:Chromatography, Thin Layer; D003460:Crystallization; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents; D007408:Intestinal Absorption; D008297:Male; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D014042:Tolazamide / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D014316:Tritium; D014961:X-Ray Diffraction
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014316:Tritium; D014042:Tolazamide