Back to Search
Start Over
Metabolic fate of tolazamide in man and in the rat
- 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.
- Subjects :
- Blood Glucose
Male
Models, Molecular
medicine.medical_specialty
Chromatography, Paper
medicine.drug_class
Metabolite
Molecular Conformation
Urine
Tritium
Mass Spectrometry
Intestinal absorption
Urine collection device
Feces
chemistry.chemical_compound
X-Ray Diffraction
Oral administration
Internal medicine
Drug Discovery
medicine
Animals
Humans
Hypoglycemic Agents
Biotransformation
Feces analysis
Tolazamide
Sulfonylurea
Rats
Endocrinology
Intestinal Absorption
chemistry
Molecular Medicine
Female
Chromatography, Thin Layer
Crystallization
medicine.drug
Subjects
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