Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency
Summary 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 profile...
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Published in | Clinical endocrinology (Oxford) Vol. 61; no. 3; pp. 367 - 375 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.09.2004
Blackwell Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
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 concentration from 31 to 7%, decreased area under the curve (AUC) from 50 to 22% (P < 0·05), and reduced overexposure to < 5%. Food taken before HC delayed its absorption. Serum cortisol measured 4 h after HC predicted cortisol AUC (r2 = 0·78; P < 0·001).
conclusions We recommend weight‐adjusted HC dosing, thrice daily before food, monitored with a single serum cortisol measurement using a nomogram. This regimen was prospectively examined in 40 cortisol‐insufficient patients, 85% of whom opted to remain on the new thrice‐daily treatment regimen. |
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Bibliography: | ark:/67375/WNG-HX42VDHK-2 istex:C696A8DE06E42AC04A8BD24F6C3E94B8D83D8151 ArticleID:CEN2106 These authors made an equal contribution. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0300-0664 1365-2265 |
DOI: | 10.1111/j.1365-2265.2004.02106.x |