Ross, R.J.M. orcid.org/0000-0001-9222-9678, Arlt, W. orcid.org/0000-0001-5106-9719, de la Perriere, A.B. et al. (13 more authors) (2025) Switching patients with congenital adrenal hyperplasia to modified‐release hydrocortisone capsules: relative bioavailability and disease control. Clinical Endocrinology. ISSN 0300-0664
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ |
Keywords: | 21-hydroxylase deficiency; adrenal insufficiency; congenital adrenal hyperplasia; glucocorticoid; hydrocortisone; MRHC |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 May 2025 14:19 |
Last Modified: | 19 May 2025 14:19 |
Status: | Published online |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/cen.15275 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:226840 |