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objective  The objective of this study was to examine the variables determining hydrocortisone (HC) disposition in patients with adrenal insufficiency and to develop practical protocols for individualized prescribing and monitoring of HC treatment.

design and patients  Serum cortisol profiles were measured in 20 cortisol‐insufficient patients (09·00 h cortisol < 50 nmol/l) given oral HC as either a fixed or ‘body surface area‐adjusted’ dose in the fasted or fed state. Endogenous cortisol levels were measured in healthy subjects. Pharmacokinetic analysis was performed using P‐Pharm software, and computer simulations were used to assess the likely population distribution of the data.

results  Body weight was the most important predictor of HC clearance. A fixed 10‐mg HC dose overexposed patients to cortisol by 6·3%, whereas weight‐adjusted dosing decreased interpatient variability in maximum cortisol …