Evaluation of the synergistic adverse effects of concomitant therapy with statins and fibrates on rhabdomyolysis

J Pharm Pharmacol. 2003 Jun;55(6):795-802. doi: 10.1211/002235703765951401.


Rhabdomyolysis is a severe adverse effect of hypolipidaemic agents such as statins and fibrates. We evaluated this muscular cytotoxicity with an in-vitro culture system. Cellular apoptosis was determined using phase-contrast and fluorescein microscopic observation with Hoechst 33342 staining. L6 rat myoblasts were treated with various statins and bezafibrate under various conditions. With statins only, skeletal cytotoxicity was ranked as cerivastatin > fluvastatin > simvastatin > atorvastatin > pravastatin in order of decreasing potency. Combined application of fibrates enhanced atorvastatin-induced myopathy, which causes little apoptosis alone. These results suggest that statins and fibrates synergistically aggravate rhabdomyolysis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bezafibrate / adverse effects*
  • Cells, Cultured
  • DNA Fragmentation
  • Drug Synergism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hypolipidemic Agents / adverse effects*
  • Lipids / biosynthesis
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • Rats
  • Rhabdomyolysis / chemically induced*
  • Structure-Activity Relationship


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipids
  • Bezafibrate