DIFFERENCES IN METABOLISM OF PREDNISOLONE-C14AND CORTISOL-C14

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Abstract
INTRODUCTION THE effectiveness in various clinical conditions of 1-dehydro-17-hydroxycorticosteroids in much smaller doses than those of cortisol or cortisone is now well established (1, 2). Little is known about the metabolic fate of these new synthetic 1-dehydrosteroids in the human body. The reasons for their greater clinical effectiveness are likewise unclear. In a previous publication it was reported that in man there are certain differences and some similarities between the metabolism of 1-dehydrocortisol and 1-dehydrocortisone (prednisolone and prednisone respectively) and the metabolism of cortisol and cortisone (17-OHCS) (3). In contrast to the latter steroids, a substantial percentage of 1-dehydrosteroid was excreted in the urine as free (unconjugated) and unchanged steroid, following either oral or intravenous administration. Only small amounts of steroids were released by β-glucuronidase hydrolysis of the urine of subjects given 1-dehydrosteroids (Δ1-17-OHCS). Furthermore, the Δ1-17-OHCS were not converted to 17-ketosteroids (17-KS) to the same extent as were the 17-OHCS. The administration of large doses (240 mg. per day) of Δ1-17-OHCS did not interfere with the normal metabolism of C14-cortisol, and the suppression of adrenal function was in all probability mediated through the pituitary gland. The clinical effectiveness of Δ1-17-OHCS was postulated to be due, at least in part, to the body's inability to metabolize them in the same manner as the 17-OHCS. The plasma concentrations of steroids, determined by the Porter-Silber reaction, were higher following the administration of prednisolone than following administration of cortisol. The rates of clearance of these steroids from the plasma were essentially similar, however. In contrast, Ely, Done and Kelley (4) reported that Δ117-OHCS were cleared from the plasma at a slower rate than cortisol, indicating a longer half-life for the former than for the latter. These authors concluded that the metabolism of 1-dehydrosteroids is slower, and postulated that this might contribute to the greater clinical effectiveness of these compounds.