Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers.
Darzy, Ken H
Shalet, Stephen M
Tucker, G T
Ross, R J M
AffiliationAcademic Unit of Diabetes, Endocrinology and Metabolism, The University of Sheffield, Sheffield, UK. email@example.com
MetadataShow full item record
AbstractBACKGROUND: All existing long-term glucocorticoid replacement therapy is suboptimal as the normal nocturnal rise and waking morning peak of serum cortisol is not reproduced. AIM: To test whether it is possible to reproduce the normal overnight rise and morning peak in serum cortisol using an oral delayed and sustained release preparation of hydrocortisone (Cortisol(ds)). SUBJECTS AND METHODS: Six healthy normal male volunteers attended on two occasions, in a single-dose, open-label, nonrandomized study. Endogenous cortisol secretion was suppressed by administration of dexamethasone. Cortisol(ds) (formulation A or B) was administered at 2200 h on day 1. Blood samples for measurement of cortisol were taken from 2200 h every 30 min until 0700 h, then hourly until 2200 h on day 2. Fifteen body mass index (BMI)-matched control subjects had serum cortisol levels measured at 20-min intervals for 24 h. Serum cortisol profiles and pharmacokinetics after Cortisol(ds) were compared with those in controls. RESULTS: Formulations A and B were associated with delayed drug release (by 2 h and 4 h, respectively), with median peak cortisol concentrations at 4.5 h (0245 h) and 10 h (0800 h), respectively, thereby reproducing the normal early morning rise in serum cortisol. Total cortisol exposure was not different from controls. CONCLUSIONS: For the first time we have shown that it is possible to mimic the normal circadian rhythm of circulating cortisol with an oral modified-release formulation of hydrocortisone, providing the basis for development of physiological circadian replacement therapy in patients with adrenal insufficiency.
CitationModified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers. 2008, 68 (1):130-5 Clin. Endocrinol.
- Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia.
- Authors: Merza Z, Rostami-Hodjegan A, Memmott A, Doane A, Ibbotson V, Newell-Price J, Tucker GT, Ross RJ
- Issue date: 2006 Jul
- Modified-release hydrocortisone to provide circadian cortisol profiles.
- Authors: Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price J, Darzy K, Merke DP, Arlt W, Ross RJ
- Issue date: 2009 May
- Effects of short-term nocturnal cortisol replacement on cognitive function and quality of life in patients with primary or secondary adrenal insufficiency: a pilot study.
- Authors: Harbeck B, Kropp P, Mönig H
- Issue date: 2009 Jun
- Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.
- Authors: Jung C, Greco S, Nguyen HH, Ho JT, Lewis JG, Torpy DJ, Inder WJ
- Issue date: 2014 Nov 26
- Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study.
- Authors: Johannsson G, Bergthorsdottir R, Nilsson AG, Lennernas H, Hedner T, Skrtic S
- Issue date: 2009 Jul