Effect of dose size on the pharmacokinetics of oral hydrocortisone suspension

The pharmacokinetics of hydrocortisone were examined following single doses of 5-, 10-, 20-, and 40-mg hydrocortisone suspensions to healthy male volunteers. Endogenous hydrocortisone was suppressed by giving 2 mg of dexamethasone the night before hydrocortisone administration. Plasma samples obtained serially for 12 hr after hydrocortisone administration were assayed by reversed-phase high-pressure liquid chromatography using a fixed-wavelength (254 nm) UV absorbance detector. Drug absorption was rapid, with mean maximum plasma hydrocortisone concentrations occurring within 60 min of dosing. Subsequent drug elimination was monophasic with mean elimination half-lives increasing from 1.2 hr for the 5-mg dose to 1.7 hr for the 40-mg dose. Increase in AUC and Cmax with increasing dose were linear but not directly proportional to dose size. This was attributed to dose-dependent absorption or to loss of drug the first-pass through the liver.