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Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses.
Olbricht, Christoph MD, PhD; Wanner, Christoph MD, PhD; Eisenhauer, Thomas MD, PhD; Kliem, Volker MD; Doll, Rainer MD; Boddaert, Michel MSc; O'Grady, Padraig PhD; Krekler, Michael PhD; Mangold, Bernhard MD, PhD; Christians, Uwe MD, PhD
[Miscellaneous Article] Clinical Pharmacology & Therapeutics. 62(3):311-321, September 1997.

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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[micro]g [middle dot] hr/L (range, 104 to 1026 [micro]g [middle dot] hr/L) after a single dose (day 1) and 241 [micro]g [middle dot] hr/L (114 to 969 [micro]g[middle dot] 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 [micro]g [middle dot] hr/L (105 to 858 [micro]g [middle dot] hr/L) on day 1 and 459 [micro]g [middle dot] hr/L (140 to 1508 [micro]g [middle dot] 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.