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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 (&lt; 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 (&lt; 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.

A Comparison of the Metabolism of Radioactive 17-Isoaldosterone and Aldosterone Administered Intravenously and Orally to Normal Human Subjects*