Rare Diseases Symptoms Automatic Extraction

Variation in Absorption and Half-life of Hydrocortisone Influence Plasma Cortisol Concentrations.

[congenital adrenal hyperplasia]

Hydrocortisone therapy should be individualised 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.48 patients (21M) aged between 6.1 and 20.3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration less than 100 nmol/l and half-life of cortisol.Mean half-life was 76.5 ± 5.2 (range 40-225.3) min, Cmax 780.7 ± 61.6 nmol/l and tmax 66.7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140- 540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34.6 min), compared to those with a slow half-life and fast tmax (298 ± 34.8 min) and those with a fast half-life and fast tmax (249.5 ± 14.4 min) (One way ANOVA F=4.52; P = 0.009) CONCLUSIONS: Both 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. This article is protected by copyright. All rights reserved.