Decreased Clearance of Prednisolone, a Factor in the Development of Corticosteroid Side Effects

Abstract

To determine if the response of a patient to synthetic corticosteroids may be influenced by its rate of catabolism, the metabolic clearance rate (MCR) and serum half-life (t½) of prednisolone were measured in 13 patients being treated with prednisone and in 7 normal subjects. Tritiated prednisolone was studied since it is the metabolically active form to which administered prednisone is rapidly converted. Steroid side effects, hirsutism and facial and truncal obesity, correlated with a slow rate of prednisolone catabolism. Prednisolone t½ was longer (246 ± 13 min vs 175 ± 17 min, p < 0.001) and MCR lower (59 ± 3 1/24 hr/m²vs 97 ± 6, p < 0.001) in patients who developed side effects than in those who did not. Therapeutic response did not correlate with the rate of catabolism of prednisolone. There was no difference in t½ (202 ± 15 min vs 238 ± 24) or in MCR (76 ± 10 1/24 hr/m²vs 71 ± 8) between patients who responded to treatment and those who did not. The data suggest that patients who develop side effects on synthetic corticosteroid treatment may be those who fail to adapt to such treatment by increasing their rate of catabolism of the administered corticosteroid.