title: Improving effect of ethyl eicosapentanoate on statin-induced rhabdomyolysis in Eisai hyperbilirubinemic rats.
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.
authors.affiliation: Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Naba
authors.forename: Chihaya
authors.initials: C
authors.lastname: Kakinuma
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Takuo
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006932:Hyperbilirubinemia / Q000150:complications* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D017035:Pravastatin; D051381:Rats; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology* / Q000517:prevention & control*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D017035:Pravastatin