Metabolism of prednisone in kidney transplanted patients with necrosis of the femoral head.

Interindividual variation of the metabolism of prednisolone and of the susceptibility to glucocorticoids might be possible factors contributing to the development of osteonecrosis after renal allotransplantation. As this aspect has not been properly investigated previously, we compared, in the present study, the metabolism of total and free prednisolone in 6 renal allotransplanted patients who subsequently developed osteonecrosis of the femoral head and the metabolism of 6 matched controls, who did not develop osteonecrosis. There was no difference in age, bodyweight, total serum protein or albumin, or in liver or renal function. The baseline cortisol was 54 +/- 23 micrograms in patients with necrosis, and 102 +/- 53 micrograms/l in patients without necrosis (n.s.). Likewise there was no difference in the peak concentration of prednisolone (420 +/- 43 vs. 394 +/- 42 micrograms/l, n.s.), the bioavailability (0.57 +/- 0.09 vs. 0.61 +/- 0.05, n.s.) or in the apparent volume of distribution at steady state (Vdss, 0.37 +/- 0.09 vs. 0.37 +/- 0.04 l/kg, n.s.). The clearance of prednisolone in patients with osteonecrosis was 33% lower (0.79 +/- 0.11 vs. 1.18 +/- 0.13 ml/min./kg b.wt., P < 0.05) and t1/2 was correspondingly 33% longer (246 +/- 18 min. vs. 184 +/- 15 min., P < 0.05) than in patients without osteonecrosis. However, there was no difference in the apparent volume of distribution of free prednisolone (2.07 +/- 0.36 vs. 1.69 +/- 0.28 l/kg, n.s.), in the t1/2 (152 +/- 30 vs. 107 +/- 20 min., n.s.), or in the clearance (7.33 +/- 2.12 vs. 7.82 +/- 1.18 ml/min./kg) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)