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Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic
Gudmundur Johannsson1, Ragnhildur Bergthorsdottir, Anna G Nilsson
1Department of Endocrinology, Sahlgrenska Academy, Sahlgrenska University Hospital, Grona Straket 8 Clinical Pharmacology, Sahlgrenska Academy, Gothenburg University, SE-413 45 Gothenburg, Sweden. gudmundur.johannsson@gu.se
European Journal of Endocrinology
|April 23, 2009
Summary
This study developed a novel dual-release hydrocortisone tablet for cortisol replacement therapy. The formulation successfully mimics the natural diurnal cortisol profile with once-daily dosing, improving patient outcomes.
Area of Science:
- Pharmacology
- Endocrinology
- Drug Delivery Systems
Background:
- Endogenous plasma cortisol exhibits a distinct circadian rhythm.
- Current cortisol replacement therapy often fails to replicate this natural diurnal variation.
- Developing a once-daily oral formulation to mimic physiological cortisol profiles is crucial.
Purpose of the Study:
- To assess the pharmacokinetics and dose-proportionality of a novel dual-release hydrocortisone tablet.
- To evaluate the effect of food intake on the 20 mg dual-release hydrocortisone formulation.
- To determine if the dual-release formulation can replicate the diurnal cortisol profile.
Main Methods:
- A randomized, controlled, cross-over, double-blind, Phase I study was conducted.
- Healthy volunteers received single oral doses of 5 mg and 20 mg dual-release hydrocortisone.
- Pharmacokinetic analysis included a fed state assessment for the 20 mg dose using LC-MS/MS and immunoassay.
Main Results:
- The dual-release hydrocortisone tablet achieved therapeutic cortisol levels (>200 nmol/l) within 20 minutes, peaking at 50 minutes.
- Cortisol levels remained elevated for approximately 6 hours, with concentrations below 50 nmol/l at 18-24 hours post-dose.
- Food intake delayed the time to reach therapeutic concentrations, and the dose-exposure relationship was not fully proportional.
Conclusions:
- The once-daily dual-release hydrocortisone tablet effectively mimics the physiological diurnal plasma cortisol profile.
- This formulation represents a significant advancement in cortisol replacement therapy.
- Further studies are warranted to confirm efficacy and safety in patient populations.
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