Thomas R C, Duchamp D J, Judy R W, Ikeda G J
J Med Chem. 1978 Aug;21(8):725-32. doi: 10.1021/jm00206a002.
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.
使用氚标记的甲苯磺丁脲（1），对1-(六氢氮杂环庚烷-1-基)-3-对甲苯磺酰脲（甲苯磺丁脲，1）在人和大鼠体内的代谢命运进行了研究。从尿液中分离出代谢物的结晶形式用于结构测定。其中一种代谢物，1-(4-羟基六氢氮杂环庚烷-1-基)-3-对甲苯磺酰脲（5）的晶体结构和最终分子结构通过单晶X射线技术确定。给男性受试者口服氚标记的甲苯磺丁脲后，在5天内85%的放射性在尿液中排出。除了以原形经尿液排出外，甲苯磺丁脲在人体内还代谢为1-(六氢氮杂环庚烷-1-基)-3-对-(羧基苯基)磺酰脲（2）、对甲苯磺酰胺（3）、1-(六氢氮杂环庚烷-1-基)-3-对-(羟甲基苯基)磺酰脲（4）、1-(4-羟基六氢氮杂环庚烷-1-基)-3-对甲苯磺酰脲（5）以及一种不稳定的、未鉴定的代谢物6。从八名受试者收集的0 - 24小时尿液中排出的这些物质的相对量，1 - 6分别平均为7%、17%、26%、10%、25%和15%。在雌性大鼠中，口服氚标记的甲苯磺丁脲剂量的79%在5天内以1 - 4的形式经尿液排出。给予甲苯磺丁脲后24小时内排出的这些物质的相对量，1 - 4分别为10%、5%、5%和80%。
