Prednisolone Replacement Therapy Mimics the Circadian Rhythm More Closely Than Other Glucocorticoids

Background: This study examined the pharmacokinetic profile of prednisolone. Methods: Using a newly developed ultra-performance liquid chromatography MS/MS method, prednisolone profiles in healthy volunteers and patients with adrenal insufficiency already treated with prednisolone were prospectively analyzed in a tertiary center. Results: Twelve prednisolone day curves were analyzed. Six patients with secondary adrenal insufficiency provided 7 curves and 3 healthy volunteers provided 5 curves, 1 of which was with the prednisolone administered in divided doses. The mean prednisolone dose required for adequate replacement in hypoadrenal patients was 3.86 mg. The overall mean maximal serum concentration (C-max) was 114.0 mu g/L and was achieved at an average time to maximal concentration (T-max) of 1.43 h. Total glucocorticoid exposure was represented by the mean area under the curve to 24 h (AUC(0-24h)), which was 518.2 mu g vertical bar.vertical bar h/L. Splitting the dose substantially increased the total glucocorticoid exposure. Conclusions: The pharmacokinetic profile of prednisolone is similar to the published profile of dual-release hydrocortisone. Once-daily prednisolone can thus be used as a replacement for hydrocortisone. Further studies need to be carried out to accurately calculate an equivalent replacement dose. Prednisolone levels are a useful adjunct to dose adjustment when low doses are being used for replacement.