Variation in absorption and half-life of hydrocortisone: a need to consider plasma terminal half-life in dosing schedules

Abstract

METHODS Congenital adrenal hyperplasia (CAH) due to a deficiency in the enzyme 21-hydroxylase (P450c21) is the commonest form of CAH. The conventional treatment of the condition uses hydrocortisone as a replacement glucocorticoid along with 9 alpha-Fludrocortisone as the mineralocorticoid replacement. Hydrocortisone is usually given in a three times per day regimen although in infancy and in puberty a four times per day regimen is more common. The concentration of cortisol resulting from the administration of hydrocortisone is dependent on the absorption of hydrocortisone from the gastrointestinal tract, balanced against the clearance of cortisol from the circulation. Although there are other components operative, such as the enterohepatic circulation, cortisol concentrations in the circulation can be conceived as a balance between the two parameters absorption and clearance. Clearance of cortisol from the circulation can be measured by an intravenous bolus administration of hydrocortisone, whereas absorption can be determined from a series of pharmacological parameters, such as the maximum concentration attained (Cmax) and the time to peak concentration (tmax). The conventional replacement dosing when using hydrocortisone is calculated on a body size basis. Other than this very little attention has been paid to individualise the dosing schedule using measures of absorption and clearance.