Recently, Pickup, Lowe & others (1977) demonstrated that the plasma clearance was elevated with increasing intravenous doses of [3H]prednisolone phosphate. We have observed similar dose-dependent pharmacokinetics of prednisone and its active metabolite prednisolone following oral administration of prednisone in humans. Eight normal healthy male volunteers participated in the study, during which each subject received oral doses of 10 or 20 mg prednisone in 5 % aqueous ethanol according to a cross-over design. Plasma samples, obtained at 0.25, 1, 2, 3, 4, 6, 8 and 12 h post administration, were evaluated for prednisone and prednisolone content by a radio-immunological assay which incorporated a procedure (Loo, Vilim & others, 1976) to remove interfering endogenous cortisol. The specificity of the assays was confirmed by high performance liquid chromatographic procedure. (Loo, Butterfield & others 1977; Loo &Jordan, 1977). The results presented in Table 1 include the mean areas under the plasma drug concentration vs timecurve to 12 h normalized to 10 mg dose (AUC) and the mean clearance values (CI) from the present study together with those reported by Pickup & others (1977). The AUC for prednisolone for the 20 mg dose was 77.8% of that for the 10 mg dose (significant P = 0.05) and the corresponding AUC for prednisone for the high dose was 87.6% that of the low dose (significant P =-O.lO). The mean clearance values of prednisolone for the 20 mg dose (0.134 mg kg-') and 10 mg dose (0.268 mg kg-') were 0.10 and 0.13 litres kg-' respectively. These apparent clearance values which are in good agreement with those reported by Pickup & others (1977), indicate that the dose-dependent effect occurs following oral administration of prednisone. As noted by the previous authors, it is probably a binding effect. June 9, 1978