Evidence that cyclosporine does not affect the metabolism of prednisolone after renal transplantation.

The following investigation was performed to establish whether renal transplant patients treated with cyclosporine and prednisone have a decreased prednisolone catabolism and/or an increased systemic availability of oral prednisone when compared with patients treated with azathioprine and prednisone. Therefore we assessed, by HPLC and equilibrium dialysis, the total concentrations of prednisolone and prednisone and the unbound concentrations of prednisolone in plasma samples collected over 24 hr, and the 24-hr urinary excretion of prednisolone, prednisone, and 6 beta-hydroxyprednisolone after an i.v. dose of prednisolone and an equal oral dose of prednisone in 25 renal transplant patients on cyclosporine and in 25 patients on azathioprine and prednisone one month after transplantation. The metabolic clearance, the renal clearance, the volume of distribution, and the systemic availability of total and unbound prednisolone were identical in patients with and without cyclosporine. The apparent activities of the oxidoreductases involved in the biotransformation of prednisone into prednisolone and vice-versa were not affected by cyclosporine therapy. The fractional urinary excretions of 6 beta-hydroxyprednisolone increased with increasing metabolic clearance rate of prednisolone (r = 0.50, P less than 0.001). This relationship was not modulated by cyclosporine, indicating that cyclosporine does not affect the activity of the microsomal P-450-dependent 6 beta-hydroxylase. Thus, early after transplantation, patients on cyclosporine have a normal metabolism of prednisolone.