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Biochemical and Biophysical Research Communications
Volume 340, Issue 1, 3 February 2006, Pages 215-220
 
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doi:10.1016/j.bbrc.2005.11.179    How to Cite or Link Using DOI (Opens New Window)
Copyright © 2005 Elsevier Inc. All rights reserved.

Improving effect of ethyl eicosapentanoate on statin-induced rhabdomyolysis in Eisai hyperbilirubinemic rats

Hiroyasu Naba, Chihaya Kakinuma, Shuhei Ohnishi and Takuo OgiharaCorresponding Author Contact Information, E-mail The Corresponding Author

Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan

Received 12 November 2005. 
Available online 9 December 2005.

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Abstract

The effect of ethyl eicosapentanoate (EPA-E) on statin-induced rhabdomyolysis was investigated by co-administration of EPA-E and pravastatin (PV), as a typical statin, to Eisai hyperbilirubinemic rats (EHBR). It was confirmed that the plasma PV concentration was not affected by simultaneous administration of EPA-E, and there was no cumulative increase of PV during prolonged co-administration of EPA-E and PV. Muscular degeneration was prominent (incidence 5/5; average grade 3.5 (range 2–4)) in EHBR treated with PV alone at 200 mg/kg/day for 14 days, but co-administration of EPA-E at doses of 100, 300, and 1000 mg/kg/day decreased the average grades to 1.4 (range 0.3–3.0), 0.5 (0.2–1.0), and 0.6 (0.0–1.7), respectively. Creatine phosphokinase (CPK) and myoglobin levels in plasma were well correlated with the grade of skeletal muscle degeneration. Thus, EPA-E appears to reduce the severity of statin-induced rhabdomyolysis.

Keywords: Statin; Ethyl eicosapentanoate; EPA-E; Rhabdomyolysis; Myopathy; Pravastatin; EHBR

Article Outline

Materials and methods
Results
Toxicokinetics of PV
Toxicity of PV
Discussion
References




 
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