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Published on: August 23, 2019
Modified-release hydrocortisone to provide circadian cortisol profiles
Miguel Debono1, Cyrus Ghobadi, Amin Rostami-Hodjegan
1Academic Unit of Diabetes, School of Medicine, Royal Hallamshire Hospital, University of Sheffield, Sheffield S10 2JF, United Kingdom.
The Journal of Clinical Endocrinology and Metabolism
|February 19, 2009
Summary
Modified-release hydrocortisone (MR-HC) can replicate the body's natural cortisol rhythm. This new formulation offers a more physiological approach to cortisol replacement therapy, improving patient outcomes.
Area of Science:
- Endocrinology
- Pharmacokinetics
- Chronobiology
Background:
- Cortisol exhibits a distinct circadian rhythm, crucial for metabolic health.
- Disruption of this rhythm is linked to fatigue and metabolic abnormalities.
- Standard glucocorticoid therapy fails to mimic physiological cortisol patterns.
Purpose of the Study:
- Define key parameters of the physiological cortisol rhythm.
- Evaluate modified-release hydrocortisone (MR-HC) for its ability to provide circadian cortisol profiles using pharmacokinetic modeling.
Main Methods:
- Defined cortisol rhythm parameters using data from 33 healthy subjects.
- Compared MR-HC with immediate-release hydrocortisone in 28 healthy volunteers via a randomized, single-dose, cross-over study.
- Utilized pharmacokinetic modeling to determine optimal MR-HC dosing regimens.
Main Results:
- Established physiological cortisol profile variables including peak, acrophase, nadir, and quiescent phase.
- MR-HC 15 mg showed delayed, sustained release, achieving a peak concentration of 16.6 μg/dL.
- Pharmacokinetic modeling indicated MR-HC dosing regimens could reproduce physiological cortisol levels.
Conclusions:
- Physiological cortisol rhythm parameters have been defined.
- Modern formulation technology enables more physiological circadian cortisol replacement with MR-HC.
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