A COMPARATIVE STUDY OF THE METABOLISM OF HYDROCORTISONE AND PREDNISOLONE*

Abstract

Intravenous infusions of the suc-cinate esters of hydrocortisone and prednisolone were given to normal subjects and to patients with hepatic or renal disease in order to study the basis for the differing glucocorticoid effectiveness of the compounds. The plasma half-time of free 17-hydroxycorticosteroids after intravenous administration of hydrocortisone esters to normal young men was 113 minutes. The plasma half-time of free 17-hydroxycorticosteroids after intravenous administration of prednisolone esters was 204 to 241 minutes in normal subjects and in patients with renal or hepatic disease. The fact that prednisolone has a longer plasma half-time than hydro-cortisone gives no clear insight into the reasons for the increased glucocorticoid effects of prednisolone compared to equivalent amounts of hydrocortisone, and their roughly similar effects on salt metabolism. The contrast in the action of the two compounds must depend on their intrinsic structures or on their different pathways of metabolism. Liver disease caused only slight delay in plasma removal of 17-hydroxycorticosteroids after prednisolone in contrast to the marked prolongation that occurs after hydrocortisone. Although patients with renal disease excreted only small amounts of free 17-hydroxycorticosteroids in their urine after intravenous prednisolone, the plasma half-time was not decreased. The rate of fall of plasma free 17-hydroxycorticosteroids after intravenous prednisolone is determined in large part by the rate of removal by organs outside the liver or kidney.