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 ph armacodynamic effects and their interactions with cyclosporine (INN, c iclosporin) in kidney transplant patients after single and multiple do ses. Subjects and methods: The pharmacokinetic and pharmacodynamic eff ects of administration of 20 mg/day oral pravastatin and lovastatin fo r 28 days and their interactions with cyclosporine (2 to 6 mg/kg/day) were studied in a double-blind, double-dummy, randomized, parallel-gro up multicenter trial in 44 stable kidney graft recipients. Results: Th e median area under the curve [AUC(0-24)] of pravastatin was 249 mu g. hr/L (range, 104 to 1026 mu g.hr/L) after a single dose (day 1) and 24 1 mu g.hr/L (114 to 969 mu g.hr/L) after multiple doses (day 28) and w as fivefold higher than values reported in the absence of cyclosporine , The median AUC(0-24) of lovastatin was 243 mu g.hr/L (105 to 858 mu g.hr/L) on day 1 and 459 mu g.hr/L (140 to 1508 mu g.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 r eported without cyclosporine, Coadministration of pravastatin or lovas tatin did not alter cyclosporine pharmacokinetics, In this study, 20 m g/day doses of both drugs resulted in a significant improvement of the lipid profile and were well tolerated. Conclusions: In contrast to lo vastatin, pravastatin did not accumulate over the study period, which is probably one of the reasons rhabdomyolysis has been reported in lov astatin-treated but not pravastatin-treated transplant patients receiv ing cyclosporine immunosuppression.