Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)

Figures

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  Fig.1. Study design. Abbreviations: SID, semel in die; BID, bis in die.

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  SupplementaryFig.1. 18-HEPE chromatograms. 18-HEPE MRM (317/255) chromatograms of the reference standard in plasma (A) and a representative plasma specimen (B). 18-HEPE MRM (317/215) chromatograms of the reference standard in culture supernatant (C) and a representative culture supernatant specimen (D).

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  SupplementaryFig.2. 17,18-EpETE chromatograms. 17,18-EpETE MRM (317/215) chromatograms of the reference standard in plasma (A) and a representative plasma specimen (B). 17,18-EpETE MRM (317/215) chromatograms of the reference standard in culture supernatant (C) and a representative culture supernatant specimen (D).

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  SupplementaryFig.3. RvE1 chromatograms. RvE1 MRM (349/107) chromatograms of the reference standard in plasma (A) and a representative plasma specimen (B). RvE1 MRM (349/107) chromatograms of the reference standard in culture supernatant (C) and a representative culture supernatant specimen (D).

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  Fig.2. Plasma total EPA concentration and EPA/AA ratio. Abbreviations: EPA, eicosapentaenoic acid; AA, arachidonic acid. The upper figures show the plasma total EPA concentrations and changes from baseline. The lower figures show the plasma EPA/AA ratio and changes from baseline. Results are medians and interquartile ranges of eight healthy subjects. #P＜0.05 vs. the corresponding baseline levels. aP＜0.05 vs. the control group. bP＜0.05 vs. the EPA-E 1.8-g group. cP＜0.05 vs. the MND-2119 2-g group.

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  Fig.3. Plasma 18-HEPE and 17,18-EpETE concentrations. Abbreviations: 18-HEPE, 18-hydroxyeicosapentaenoic acid; 17,18-EpETE, 17,18-epoxyeicosatetraenoic acid; EPA, eicosapentaenoic acid. Results are medians and interquartile ranges of eight healthy subjects. aP＜0.05 vs. the control group. bP＜0.05 vs. the EPA-E 1.8-g group. cP＜0.05 vs. the MND-2119 2-g group.

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  SupplementaryFig.4. Association between plasma total EPA concentrations, EPA/AA ratio and 18-HEPE, 17,18-EpETE at Day 1 3 h. Abbreviations: EPA, eicosapentaenoic acid; AA, arachidonic acid. Plots show data of MND-2119 2 g group, MND-2119 4 g group and EPA-E 1.8 g group at Day 1 3 h (N=24).

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  SupplementaryFig.5. Association between plasma total EPA concentrations, EPA/AA ratio and 18-HEPE, 17,18-EpETE at Day 7 24 h. Abbreviations: EPA, eicosapentaenoic acid; AA, arachidonic acid. Plots show data of MND-2119 2 g, MND-2119 4 g and EPA-E 1.8 g group at Day 7 24 h (N=24).

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  Fig.4. Total EPA concentration in blood cells. Abbreviations: EPA, eicosapentaenoic acid; RBC, red blood cells; PBMC, peripheral blood mononuclear cells. Figures show the changes in blood cell total EPA from baseline. Results are medians and interquartile ranges of eight healthy subjects. #P＜0.05 vs. the corresponding baseline levels. aP＜0.05 vs. the control group. bP＜0.05 vs. the EPA-E 1.8-g group. cP＜0.05 vs. the MND-2119 2-g group.

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  Fig.5. Association between neutrophil total EPA concentrations and 18-HEPE production. Abbreviations: EPA, eicosapentaenoic acid; 18-HEPE, 18-hydroxyeicosapentaenoic acid. Plots represent data of all groups at Day 7 3 and 24 h (N=64).