Alteration in plasma docosahexaenoic acid levels following oral administration of ethyl icosapentate to rats

OBJECTIVES: Ethyl icosapentate, a prodrug of eicosapentaenoic acid (EPA), has been prescribed to not only hyperlipidemia, but also psychotic patients. We have examined the impact of an orally administered polyunsaturated fatty acid (PUFA), ethyl icosapentate, on the plasma concentrations of seven other types of fatty acids and one metabolite (3-hydroxybutyrate, 3-HB) using rats. DESIGN: and Methods: A commercial omega-3 PUFA, EPA, formulation (ethyl icosapentate, Epadel®) was administered orally to Sprague-Dawley rats (15, 50, 100 mg/kg, n = 4–8) and changes in the plasma fatty acid concentrations were investigated by HPLC using fluorescence detection. RESULTS: The concentration of an n-3 PUFA, docosahexaenoic acid (DHA), was significantly increased from 11.6 ± 1.45 (0 h) to 25.9 ± 6.54 μM (6 h) in rat plasma (n = 8, p = 1.88 × 10(-2)) at a dose of 100 mg/kg, as was the EPA concentration from 2.58 ± 0.16 (0 h) to 6.03 ± 2.20 μM (1 h) (n = 8, p = 2.09 × 10(-2)), whereas concentrations of other fatty acids, such as α-linolenic acid, palmitoleic acid, arachidonic acid, linolenic acid, and oleic acid, were not significantly changed. In addition, the concentration of the ultimate fatty acid metabolite, 3-hydroxybutyrate (3-HB), was significantly increased (from 94.6 ± 10.2 to 217 ± 43.4, p = 5.41 × 10(-3)) 12 h after oral administration of ethyl icosapentate (n = 8, 100 mg/kg). CONCLUSIONS: This result suggests that intake of the EPA formulation contributed not only to an increase in EPA concentration, but also to increases in DHA and 3-HB concentrations in vivo.