Studies Comparing the Metabolic Clearance Rate of 11β,17,21-Trihydroxypregn-1,4-Diene-3,20-Dione (Prednisolone) after Oral 17,21-Dihydroxypregn-l,4-Diene-3,11,20-Trione and Intravenous Prednisolone

Abstract

The MCR of prednisolone (11 beta,17,21-trihydroxypregn-1,4-diene-3,20-dione) and the absorption of prednisone (17,21-dihydroxypregn 1,4-diene-3,11,20-trione) were studied in five normal subjects and four patients. Plasma and urinary prednisolone were measured by a competitive radioassay. The MCR was determined after iv administration of 30 mg nonisotopic prednisolone using one-compartment (MCR1) and two-compartment (MCR2) analyses. These values were compared with the MCR determined after oral administration of nonisotopic prednisone (MCR0). MCR1 and MCR2 were closely correlated, indicating the applicability of first order kinetics to the study of prednisolone metabolism. In subjects with normal gastrointestinal function, MCR0 was consistently lower than MCR2 (mean MCR2 = 0.175 liters/h.kg; MCR0 = 0.145 liters/h.kg). In two patients with steroid malabsorption, the MCR0 was significantly greater than MCR2. Knowledge of the expected relationship between MCR0 and MCR2 allowed quantitation of the degree of malabsorption. With or without impaired absorption, the absorptive process was essentially complete by the time of the peak plasma concentration. Estrogen therapy lowered the MCR0, and high prednisone dose increased the MCR0. Those effects and the effects of iv prednisolone administration on the MCR are explained by the effects of plasma protein binding of prednisolone. These studies demonstrate the usefulness of the oral MCR determination in the evaluation of steroid absorption and metabolism.