ID | 65747 |
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Author |
Miyoshi, Toru
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
Naoe, Satoko
Medical Affairs Department, Mochida Pharmaceutical Co., Ltd.
Wakabayashi, Hiroyuki
Medical Affairs Department, Mochida Pharmaceutical Co., Ltd.
Yano, Takashi
Medical Affairs Department, Mochida Pharmaceutical Co., Ltd.
Mori, Takuya
Clinical Research Department, Mochida Pharmaceutical Co., Ltd.
Kanda, Shingo
Clinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd.
Arita, Makoto
Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
Ito, Hiroshi
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
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Abstract | Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119.
Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated. Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations. |
Keywords | Eicosapentaenoic acid
MND-2119
Metablolite
Inflammation
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Published Date | 2023-12-01
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Publication Title |
Journal of Atherosclerosis and Thrombosis
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Volume | volume30
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Issue | issue12
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Publisher | Japan Atherosclerosis Society
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Start Page | 1927
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End Page | 1949
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ISSN | 1340-3478
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NCID | AA11018976
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | ©2023 Japan Atherosclerosis Society
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File Version | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.5551/jat.64135
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License | https://creativecommons.org/licenses/by-nc-sa/4.0/
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