Evaluation of the synergistic adverse effects of concomitant therapy with statins and fibrates on rhabdomyolysis.
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.
Matzno
Sumio
S
School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Kyuban-cho, Koshien, Nishinomiya, Hyogo 663-8179, Japan. smatzno@mwu.mukogawa-u.ac.jp
Tazuya-Murayama
Keiko
K
Tanaka
Hiromi
H
Yasuda
Shinya
S
Mishima
Motohiro
M
Uchida
Takahiro
T
Nakabayashi
Toshikatsu
T
Matsuyama
Kenji
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001629:Bezafibrate / Q000009:adverse effects*; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004357:Drug Synergism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008055:Lipids / Q000096:biosynthesis; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012206:Rhabdomyolysis / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D001629:Bezafibrate