Fluocortolone: pharmacokinetics and effect on plasma cortisol level

Abstract

The pharmacokinetics of fluocortolone and its effect on plasma cortisol levels are described after oral administration of 20, 50 and 100 mg to 9 healthy adults. The concentrations of fluocortolone and cortisol in plasma were measured simultaneously by HPLC with UV detection. Fluocortolone was rapidly absorbed after all doses, giving the maximum plasma level after 1.4-2.1 h. After ingestion of 20, 50 and 100 mg, the peak levels were 199, 419 and 812 ng/ml, respectively. The maximum plasma levels and areas under the plasma level-time curves increased in proportion to the dose. Post-maximum plasma levels declined monoexponentially with a half-life of 1.76 h. Plasma half-life (t1/2 = 1.76 h), volume of distribution (1.03 l/kg) and oral clearance (6.9 ml/min/kg) were independent of the dose. The intensity and duration of adrenal suppression was dose dependent. Maximum suppression was observed 8 hours after fluocortolone. Clearcut suppression of cortisol levels after 24 hours was only seen following 100 mg fluocortolone.