Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency.
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.


METHODS
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 (r(2) = 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.
Mah
Peak M
PM
Division of Clinical Sciences (North), University of Sheffield, UK.
Jenkins
Richard C
RC
Rostami-Hodjegan
Amin
A
Newell-Price
John
J
Doane
Anita
A
Ibbotson
Victoria
V
Tucker
Geoffrey T
GT
Ross
Richard J
RJ
D000309:Adrenal Insufficiency / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001835:Body Weight; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D006854:Hydrocortisone