Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses

Objectives To study pravastatin and lovastatin pharmacokinetic and pharmacodynamic effects and their interactions with cyclosporine (INN, ciclosporin) in kidney transplant patients after single and multiple doses. Subjects and methods The pharmacokinetic and pharmacodynamic effects of administration of 20 mg/day oral pravastatin and lovastatin for 28 days and their interactions with cyclosporine (2 to 6 mg/kg/day) were studied in a double-blind, double-dummy, randomized, parallel-group multicenter trial in 44 stable kidney graft recipients. Results The median area under the curve [AUC(0–24)] of pravastatin was 249 μg · hr/L (range, 104 to 1026 μg · hr/L) after a single dose (day 1) and 241 μg · hr/L (114 to 969 μg · hr/L) after multiple doses (day 28) and was fivefold higher than values reported in the absence of cyclosporine. The median AUC(0–24) of lovastatin was 243 μg · hr/L (105 to 858 μg · hr/L) on day 1 and 459 μg · hr/L (140 to 1508 μg · hr/L) on day 28. Besides a significant accumulation during the study period (p < 0.001), the lovastatin AUC(0–24) values were twentyfold higher than values reported without cyclosporine. Coadministration of pravastatin or lovastatin did not alter cyclosporine pharmacokinetics. In this study, 20 mg/day doses of both drugs resulted in a significant improvement of the lipid profile and were well tolerated. Conclusions In contrast to lovastatin, pravastatin did not accumulate over the study period, which is probably one of the reasons rhabdomyolysis has been reported in lovastatin-treated but not pravastatin-treated transplant patients receiving cyclosporine immunosuppression. Clinical Pharmacology & Therapeutics (1997) 62, 311–321; doi