Title: IMPAIRMENT OF PREDNISOLONE METABOLISM BY CYCLOSPORINE TREATMENT IN RENAL GRAFT RECIPIENTS
Abstract: Pharmacokinetics of prednisolone were studied in 64 randomly chosen renal transplant patients treated with azathioprine and prednisolone (Aza-Po) or cyclosporine and prednisolone (CsA-Po). Intrinsic clearance for prednisolone was calculated after an oral test dose of 0.5 mg prednisolone/kg bodyweight. In 38 patients on Aza-Po treatment the mean clearance for prednisolone was 0.17±0.04 1/kg/hr (range 0.11–0.27) and in 39 patients on CsA-Po the mean prednisolone clearance was 0.12±0.02 (0.07–0.17) (P<0.001). Eight patients on CsA-Po were tested on three occasions; prednisolone clearance at 2–4 weeks was 0.13±0.02 (range 0.11–0.17), at 3–6 months 0.11±0.01 (0.10–0.12) and at 2–5 years 0.11± 0.02 (0.09–0.14). In 11 patients the treatment was changed from Aza-Po to CsA-Po. The prednisolone clearance then decreased from 0.18±0.05 1/kg/hr (range 0.13–0.27) to 0.12±0.03 (0.10–0.16) (P<0.001). When the treatment was changed from CsA-Po to Aza-Po in 2 patients the prednisolone clearance increased from 0.12 and 0.10 to 0.17 and 0.12 1/kg/hr, respectively. These data show not only that the prednisolone metabolism is slower in cyclosporine-treated patients but also that this metabolism is retarded when azathioprine is replaced by cyclosporine, and that it is accelerated when cyclosporine is replaced by azathioprine. In the CsA-Po treated patients the prednisolone clearance was also found to be lower after 3–6 months than after less than one month (P<0.05) but there has been no further decrease in the prednisolone metabolism after up to more than 4 years of cyclosporine treatment.