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

Clin Pharmacol Ther. 1997 Sep;62(3):311-21. doi: 10.1016/S0009-9236(97)90034-5.


Objectives: To study pravastatin and lovastatin pharmacokinetic and pharmacodynamic effects and their interactions with cydosporine (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 microg x hr/L (range, 104 to 1026 microg x hr/L) after a single dose (day 1) and 241 microg x hr/L (114 to 969 microg x 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 microg x hr/L (105 to 858 microg x hr/L) on day 1 and 459 microg x hr/L (140 to 1508 microg x 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Anticholesteremic Agents / blood
  • Anticholesteremic Agents / pharmacokinetics*
  • Area Under Curve
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics
  • Cyclosporine / therapeutic use*
  • Double-Blind Method
  • Drug Interactions
  • Drug Therapy, Combination
  • Graft Rejection / drug therapy
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / immunology*
  • Lovastatin / blood
  • Lovastatin / pharmacokinetics*
  • Middle Aged
  • Pravastatin / blood
  • Pravastatin / pharmacokinetics*


  • Anticholesteremic Agents
  • Immunosuppressive Agents
  • Cyclosporine
  • Lovastatin
  • Pravastatin