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 less than 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 less than 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 less than 0.05) but there has been no further decrease in the prednisolone metabolism after up to more than 4 years of cyclosporine treatment.
authors.affiliation: Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Ost
mesh_terms: D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D016030:Kidney Transplantation; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D011239:Prednisolone / Q000493:pharmacokinetics*
chemical_list: D003524:Cyclosporins; D011239:Prednisolone; D001379:Azathioprine