Flood C, Pincus G, Tait J F, Tait S A, Willoughby S
J Clin Invest. 1967 May;46(5):717-27. doi: 10.1172/JCI105572.
After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 +/- 0.4 (SE) and 5.4 +/- 0.5 (SE)%, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 +/- 5 (SE) and 39 +/- 4 (SE)%, respectively, was recovered as tetrahydroaldosterone after incubation with beta-glucuronidase.After intravenous and oral administration of 17-isoaldosterone-4-(14)C to a similar group of subjects, 35 +/- 3 (SE) and 53 +/- 4 (SE)%, respectively, of the dose was recovered as 17-isoaldosterone released by acid and less than 5% as total metabolites after incubation with beta-glucuronidase. No detectable radioactivity (< 0.5%) could be recovered as tetrahydroaldosterone or as a compound with the expected chromatographic properties of tetrahydro-17-isoaldosterone. The total radioactivity in the neutral extracts was also relatively small (< 2%) after administration of either labeled aldosterone or 17-isoaldosterone. The radioactivity as aldosterone in the neutral extract was much lower after oral [0.017 +/- 0.003 (SE)%] than after intravenous [0.21 +/- 0.04 (SE)%] administration of labeled aldosterone. The radioactivity as 17-isoaldosterone in the neutral extract was similar after intravenous [0.20 +/- 0.02 (SE)%] and after oral [0.38 +/- 0.18 (SE)%] administration of 17-isoaldosterone. These results indicated that, due to lack of A-ring reduction of the molecule and the consequent slowing of hepatic clearance, 17-isoaldosterone is converted to an acid-labile conjugate (presumably 17-isoaldosterone 18-glucuronide) as the major metabolite. 17-Isoaldosterone was not secreted or converted to aldosterone to any significant extent in the normal subjects investigated.
给正常受试者静脉注射和口服放射性醛固酮后，通过弱酸水解（从醛固酮18 - 葡糖醛酸苷）从48小时尿液收集中回收的剂量分别为7.3±0.4（标准误）%和5.4±0.5（标准误）%，以醛固酮形式存在；与β - 葡糖醛酸酶孵育后，分别有35±5（标准误）%和39±4（标准误）%以四氢醛固酮形式回收。给一组类似受试者静脉注射和口服17 - 异醛固酮 - 4 -（14）C后，与β - 葡糖醛酸酶孵育后，分别有35±3（标准误）%和53±4（标准误）%的剂量以17 - 异醛固酮形式回收，作为总代谢物回收的不到5%。没有可检测到的放射性（<0.5%）以四氢醛固酮或具有四氢 - 17 - 异醛固酮预期色谱特性的化合物形式回收。给予标记的醛固酮或17 - 异醛固酮后，中性提取物中的总放射性也相对较小（<2%）。口服标记醛固酮后，中性提取物中以醛固酮形式存在的放射性[0.017±0.003（标准误）%]远低于静脉注射后[0.21±0.04（标准误）%]。静脉注射[0.20±0.02（标准误）%]和口服[0.38±0.18（标准误）%]17 - 异醛固酮后，中性提取物中以17 - 异醛固酮形式存在的放射性相似。这些结果表明，由于分子缺乏A环还原以及随之而来的肝脏清除减慢，17 - 异醛固酮转化为一种酸不稳定的缀合物（可能是17 - 异醛固酮18 - 葡糖醛酸苷）作为主要代谢物。在所研究的正常受试者中，17 - 异醛固酮没有显著分泌或转化为醛固酮。
