Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations

BackgroundHydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Patients and MethodsForty-eight patients (21 M) aged between 61 and 203years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (C-max), time of maximum plasma concentration (t(max)), time to attaining plasma cortisol concentration <100nmol/l and half-life of cortisol. ResultsMean half-life was 76552 (range 40-2253) min, C-max 7807 +/- 616nmol/l and t(max) 667 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow t(max) took longest to reach a plasma cortisol concentration less than 100nmol/l (380 +/- 346min), compared to those with a slow half-life and fast t(max) (298 +/- 348min) and those with a fast half-life and fast t(max) (2495 +/- 144min) (One-way anovaF=452; P=0009). ConclusionsBoth rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals.