Association between risk of myopathy and cholesterol-lowering effect: a comparison of all statins.
In the present study, we examined the mechanisms underlying the cytotoxicity of pitavastatin, a new statin, and we compared the in vitro potencies of muscle cytotoxicity using a prototypic embryonal rhabdomyosarcoma cell line (RD cells), a typical side effect of statins and compared the cholesterol-lowering effects of statins using Hep G2 hepatoma cells. Pitavastatin reduced the number of viable cells and caused caspase-9 and -3/7 activation in a time- and concentration-dependent manner. The comparison of cytotoxities of statins showed that statins significantly reduced cell viability and markedly enhanced activity of caspase-3/7 in concentration-dependent manner. On the other hand, the effects of hydrophilic statins, pravastatin, rosuvastatin were very weak. The rank order of cytotoxicity was cerivastatin > simvastatin acid> fluvastatin > atorvastatin > lovastatin acid > pitavastatin >> rosuvastatin, pravastatin. Statin-induced cytotoxicity is associated with these partition coefficients. On the other hand, the cholesterol-lowering effect of statins did not correlate with these partition coefficients and cytotoxicity. Thus, it is necessary to consider the association between risk of myopathy and cholesterol-lowering effect of a statin for precise use of statins.
Kobayashi
Masaki
M
Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Chisaki
Ikumi
I
Narumi
Katsuya
K
Hidaka
Kazuhiro
K
Kagawa
Toshiki
T
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009135:Muscular Diseases / Q000188:drug therapy* / Q000473:pathology; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D013778:Tetrazolium Salts; D013844:Thiazoles
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D013778:Tetrazolium Salts; D013844:Thiazoles; D002784:Cholesterol; D020169:Caspases; C022616:thiazolyl blue; C108475:pitavastatin