Simvastatin-induced myopathy with concomitant use of cyclosporine: case report

Int J Clin Pharmacol Ther. 2011 Dec;49(12):772-7. doi: 10.5414/cp201623.

Abstract

Objective: Simvastatin has been shown to play an important role in reducing the risk of cardiovascular events caused by atherosclerosis. To promote the understanding of the potential toxicity of simvastatin and individualized treatment in genetic factors, we report a case of a renal transplant in a female patient who had developed acute myopathy after taking simvastatin.

Methods: By PCR restriction fragment length polymorphism (PCR-RFLP) and allele-specificity polymerase chain reaction (AS-PCR) and direct sequencing. The genotypes of CYP3AP1, CYP3A5, CYP3A4 and SLCO1B1 were analyzed.

Results and discussion: The patient was identified to have mutant genotypes of CYP3AP1*3/*3 (-44G > A), CYP3A5*3/*3 (6986A > G) and wild genotype of CYP3A4*1/*1 and SLCO1B1*1/*1, which finally led to the elevation of her cyclosporine level except the SLCO1B1*1/*1 genotype and the acceleration of simvastatin-induced acute myopathy.

Conclusion: Genetic factors have partly contributed to the development of simvastatin-induced myopathy with concomitant use of cyclosporine, and provided information on the adverse reactions of statins. What is different from other studies is that the SNP of SLCO1B1*5 does not take part in this adverse reaction.

Publication types

  • Case Reports

MeSH terms

  • Cyclosporine / adverse effects*
  • Cyclosporine / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Drug Interactions
  • Female
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Immunosuppressive Agents / adverse effects*
  • Kidney Transplantation
  • Liver-Specific Organic Anion Transporter 1
  • Middle Aged
  • Muscular Diseases / chemically induced
  • Organic Anion Transporters / genetics
  • Simvastatin / adverse effects*
  • Simvastatin / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunosuppressive Agents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Cyclosporine
  • Simvastatin
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A