Abstract
Three fasted, male subjects received single 10-, 30-, and 50-mg oral doses of hydrocortisone tablets on separate occasions. Endogenous hydrocortisone was suppressed by giving 2mg of dexametha-sone 9hr prior to dosing. Plasma samples obtained serially for 8hr after hydrocortisone dosing were assayed by reversed-phase high-pressure liquid chromatography (HPLC) with UV detection and by normal-phase HPLC with fluorescence detection of the dansylhydrazine derivative of hydrocortisone. The two assay methods yielded equivalent plasma hydrocortisone concentrations. Metabolite interference was absent in both assay methods. Drug concentrations in plasma from all three doses of hydrocortisone were described by one-compartment open-model kinetics, with first-order absorption and elimination, and an absorption lag time. Mean Cmax values of 199, 393, and 419 ng/ml were obtained at 1.0, 1.0, and 1.7hr following the 10-, 30-, and 50-mg doses, respectively. Hydrocortisone was cleared from plasma with an elimination half-life of ~1.5hr. Within the dosage range studied, plasma levels of hydrocortisone were related, but not directly proportional, to dose size. This apparent lack of proportionality may be due to reduced drug availability or altered distribution with increasing dose.
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