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

ABSTRACT: 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??M (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??M (1?h) (n?=?8, p?=?2.09?×?10-2), whereas concentrations of other fatty acids, such as ?-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.

SUBMITTER: Onozato M

PROVIDER: S-EPMC6838527 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Onozato Mayu M Okanishi Yukina Y Akutsu Misumi M Okumura Ikumi I Nemoto Aina A Takano Kyosuke K Sakamoto Tatsuya T Ichiba Hideaki H Fukushima Takeshi T

Practical laboratory medicine 20191024

<h4>Objectives</h4>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.<h4>Design</h4>and Methods: A commercial omega-3 PUFA, EPA, formulation (ethyl icosapentate, Epadel®) was admini ...[more]

PMID: 31720355

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Project description:3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African-American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two-dimensional gas chromatography-mass spectrometry. Specimens were collected up to 3 h post-dose and evaluated for maximum concentration (C max), first detection time (t first), time of C max (t max), and 3-h area under the curve (AUC0-3 h); as well as blood metabolite ratios and blood/plasma ratios. Median blood MDMA and MDA C max were significantly greater (p?<?0.0005) than in plasma, but HMMA was significantly less (p?<?0.0005). HMA was detected in few blood specimens, at low concentrations. Nonlinear pharmacokinetics were not observed for MDMA or MDA in this absorptive phase, but HMMA C max and AUC0-3 h were similar for both doses despite the 1.6-fold dose difference. Blood MDA/MDMA and MDA/HMMA significantly increased (p?<?0.0001) over the 3-h time course, and HMMA/MDMA significantly decreased (p?<?0.0001). Blood MDMA C max was significantly greater in females (p?=?0.010) after the low dose only. Low-dose HMMA AUC0-3 h was significantly decreased in females' blood and plasma (p?=?0.027) and in African-Americans' plasma (p?=?0.035). These data provide valuable insight into MDMA blood-plasma relationships for forensic interpretation and evidence of sex- and race-based differential metabolism and risk profiles. Figure Median (interquartile range) blood/plasma 3,4-methylenedioxymethamphetamine (MDMA) (a), 4-hydroxy-3-methoxymethamphetamine (HMMA) (b), and 3,4-methylenedioxyamphetamine (MDA) (c) ratios for 3 h after controlled MDMA administration. Changes over time were significant after the 1.6 mg/kg dose for HMMA and MDA (p?=?0.013 and p?=?0.021), but not for MDMA. No changes over time were significant after the 1.0 mg/kg dose. Note: y-axes do not begin at 0. *p ?<?0.05 (low vs. high).

Dataset Information

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

Publications

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

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