Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin

Nephron. 1993;65(3):410-3. doi: 10.1159/000187521.


A few cases of severe rhabdomyolysis have been reported in heart transplant recipients treated simultaneously with ciclosporin (CS) and the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin. When measured, plasma lovastatin HMG-CoA reductase inhibitor concentrations in these patients were higher than expected. This prompted us to study the plasma concentration profiles of simvastatin HMG-CoA reductase inhibitory activity after a single dose of simvastatin in kidney transplant recipients. Five patients treated with CS, azathioprine and prednisolone (CS patients) were compared to 5 patients treated with azathioprine and prednisolone (non-CS patients). The concentration curves had similar shapes but the mean area under the curve/24 h was almost 3 times higher (p = 0.047) and the mean peak concentration was twice as high in CS patients (p = 0.028). These results suggest a difference in the disposition of simvastatin in CS patients as compared to non-CS patients. Simvastatin should be administered in a reduced dosage to CS patients.

MeSH terms

  • Adult
  • Aged
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects*
  • Drug Interactions
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / physiology
  • Lovastatin / administration & dosage
  • Lovastatin / adverse effects
  • Lovastatin / analogs & derivatives*
  • Lovastatin / blood
  • Male
  • Middle Aged
  • Rhabdomyolysis / chemically induced
  • Simvastatin


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cyclosporine
  • Lovastatin
  • Simvastatin