Endocrine Abstracts

Novel biopharmaceutical techniques have allowed the development of a hydrocortisone modified release (MR) tablet (once-daily administration for replacement therapy in adrenal insufficiency) mimicking more closely the physiological serum cortisol profile. Robust bioavailability is needed to secure this new treatment safety.Aims: To compare single-dose pharmacokinetics (PK) of MR tablets manufactured at two different sites by assessing intra-subject variab...

Volume 82, Issue 1, January 2015, Pages 2–11. DOI: 10.1111/cen.12603...

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 incr...

Background: Mortality rate in patients with primary and secondary adrenal insufficiency is increased. A contributing factor could be the dose and the pattern of glucocorticoid replacement therapy. Hydrocortisone administered twice or thrice daily produces high serum peaks and low trough values in-between. A novel, once daily, hydrocortisone modified release tablet with combined immediate and extended release characteristics was developed.Purpose: The aim...

Introduction: Glucocorticoid replacement for adrenal insufficiency (AI) remains inadequate, resulting in high morbidity, premature mortality and quality-of-life (QoL) impairment. This study investigated the long-term safety of dual-release hydrocortisone (DR-HC) in patients with primary AI.Methods: AI patients who completed a randomized, 3-month crossover study of once-daily DR-HC versus thrice-daily conventional immediate-release hydrocortisone plus a 6...

Introduction: Oral once-daily dual-release hydrocortisone (DR-HC) therapy provides a more physiological cortisol profile than conventional thrice-daily (TID) replacement therapy and has demonstrated improved metabolic profile among patients with adrenal insufficiency (AI). The mechanisms by which this metabolic improvement occurs may be due to less total exposure, changed cortisol time exposure profile, but also modified metabolism of cortisol.Objective:...

Introduction: Primary adrenal insufficiency (PAI) leads to a drastically reduced production of steroids from the adrenal cortex, but a few patients may keep some residual adrenal steroid secretion that may simplify replacement therapy and prevent adrenal crisis. Irrespectively, the conventional glucocorticoid (GC) replacement therapy, using thrice-daily oral hydrocortisone, does not restore the patients’ physiological cortisol profile.Objective: The...