Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 P24 | DOI: 10.1530/endoabs.32.P24

ECE2013 Poster Presentations Adrenal cortex (64 abstracts)

Management of Addison's disease patients using dual release hydrocortisone during periods of intercurrent illness

Ulrika SH Simonsson 1 , Stanko Skrtic 2 , Hans Lennernäs 3 , Claudio Marelli 4 & Gudmundur Johannsson 5


1Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; 2Department of Clinical Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Pharmacy, Uppsala University, Uppsala, Sweden; 4ViroPharma SPRL, Maidenhead, UK; 5Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.


Introduction: Current management of intercurrent illness (ICI) in adrenal insufficiency (AI) is inadequate. We attempted to optimise ICI regimens with pharmacokinetic simulations of a dual-release (DR) hydrocortisone (HC) and tested them in a formal clinical trial.

Methods: This work consisted of: i) dosing recommendations in episodes of mild ICI with DR-HC using simulations with a population pharmacokinetic model, ii) collection of ICI episodes with increased cortisol use and outcome assessment using quality-of-life (QoL; Fatigue Impact Scale, Short-Form 36), and iii) exposure-response model for probability of developing an ICI based on logistic regression.

Data was collected from a 3-month cross-over trial comparing once-daily DR-HC with immediate-release (IR) HC given TID using the same daily dose of HC. Further safety data for DR-HC were available for 80 patients over 27 months.

Results: Cortisol profiles were obtained in 62 patients after administration of DR-HC on 116 occasions, and in 16 healthy volunteers. Simulations showed that an additional DR-HC dose at 8±2 h after the morning dose or TID with 8 h intervals provided greater 24 h coverage IR-HC TID.

There was no difference in ICI episodes between DR-HC and IR-HC in mean percentage of days with extra doses, 2.5 and 1.6% respectively (median both 0.0). QoL after an ICI episode was not different between DR-HC and IR-HC. The total experience with DR-HC in mild ICI corresponded to 145 patient years (293 episodes).

There was no correlation between total HC exposure (AUC 0–24 h) and numbers of AEs The estimated probability of at least one adverse event episode was not associated with total (AUC 0–24 h) HC exposure; DR-HC (P=0.64) and IR-HC (TID) (P=0.52).

Conclusions: In this first prospective study in ICI, the suggested DR-HC regimens were successfully implemented in the clinical management of AI patients. Simulations suggested DR-HC regimens gave greater coverage over 24 h than IR-HC.

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