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 (Cmax) was 114.0 μg/L and was achieved at an average time to maximal concentration (Tmax) of 1.43 h. Total glucocorticoid exposure was represented by the mean area under the curve to 24 h (AUC0–24h), which was 518.2 μg|·|h/L. Splitting the dose substantially increased the total glucocorticoid exposure. Conclusions: The pharmacokinetic profile of prednisolone is similar to the published profile of dualrelease 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.