Pharmacokinetics of Dietary 13 C‐labeled Icosapentaenoic Acid in Japanese Flounder Paralichthys olivaceus

The objectives of this study were to investigate: 1) the pharmacokinetics of dietary icosapentaenoic acid (EPA) in the plasma using 13 C‐labeled EPA ([ 13 C]EPA); 2) the bioavailability of [ 13 C]EPA with different chemical forms; and 3) an effective plasma EPA level for normal growth of the Japanese flounder Parachthys olivaceus . [ 13 C]EPA was biosynthesized using the Chlorella Nannochloropsis oculate , and 1‐myristoyl 2‐[ 13 C]icosapentaenoyl phasphatidyl‐choline ([ 13 C]EPA‐PC) and [ 13 C]EPA ethyl ester ([ 13 C]EPA‐EE) were chemically synthesized from [ 13 C]EPA. Free [ 13 C]EPA ([ 13 C]EPA‐FREE) dissolved in 0.5% tragacanth gum‐polye‐thyleneglycol (3:1, V/V) was administered to the Japanese flounder at dosages of 2.8, 5.6, and 16.8 mg/kg by a single oral administration. [ 13 C]EPA‐PC (44.8 mg/kg) and [ 13 C]EPA‐EE (18.3 mg/kg), equimolar to 3.0 mg [ 13 C]EPA‐FREE (16.8 mg/kg), were administered to the fish in a similar manner. In [ 13 C]EPA‐FREE dosed fish, the kinetics of the mean plasma [ 13 C]EPA were linear with respect to dose. [ 13 C]EPA‐FREE and [ 13 C]EPA‐PC were more efecient in maintaining high plasma EPA levels than [ 13 C]EPA‐EE in the Japanese flounder. [ 13 C]EPA was distributed in plasma, blood cell, eyeball containing the orbital fat, liver, stomach, intestine, skin, brain, heart and muscle in three [ 13 C]EPA derivatives studies. The effective plasma EPA level for normal growth of the Japanese flounder is estimated to be 307 to 937 μg/mL for EPA‐FREE administration, and from 286 to 815 μg/mL 6.3 to 38 mg/mL for the EPA‐PC administration.