Ross, Richard John M., Arlt, Wiebke, de la Perriere, Aude Brac, Hirschberg, Angelica Lindén, Juul, Anders, Merke, Deborah P., Newell‐Price, John D. C., Prete, Alessandro, Rees, D. Aled ![]() ![]() |
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Abstract
Background: Replacement therapy with modified‐release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH). Aims: To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC. Methods: (1): Crossover study in healthy participants comparing relative bioavailability of MRHC with immediate‐release hydrocortisone (IRHC). (2): Post hoc analysis of first 4 weeks of phase 3 MRHC study when CAH patients were switched to MRHC. Results: Twenty‐four healthy male participants completed the relative bioavailability study: 20 mg MRHC showed comparable bioavailability to 20 mg IRHC tablets; mean AUC0−inf was 2650 versus 2450 h*nmol/L, ratio of 108% (90% confidence interval (CI) 103%−113%). In the phase 3 study, 122 CAH patients were recruited of which 63 patients were managed with IRHC alone at baseline; 31 of 63 were randomised to continue IRHC and 32 of 63 were randomised to switch to MRHC on the same daily dose but given twice daily. At 4 weeks, a greater reduction in both the 09:00 h 17‐hydroxyprogesterone and androstenedione was observed in the MRHC group compared to the IRHC group; p < 0.001 and p = 0.01, respectively. Conclusions: MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20 mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment.
Item Type: | Article |
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Date Type: | Published Online |
Status: | In Press |
Schools: | Schools > Medicine |
Additional Information: | License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/ |
Publisher: | Wiley |
ISSN: | 0300-0664 |
Date of First Compliant Deposit: | 20 May 2025 |
Date of Acceptance: | 8 May 2025 |
Last Modified: | 20 May 2025 10:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/178369 |
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