title: Relative Bioavailability of an Emulsion Formulation for Omega-3-Acid Ethyl Esters Compared to the Commercially Available Formulation: A Randomized, Parallel-Group, Single-Dose Study Followed by Repeat Dosing in Healthy Volunteers.
abstract: LOVAZA (omega-3-acid ethyl esters; eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]), with diet, lowers very high triglycerides (≥500 mg/dL) in adults. This study evaluated whether an emulsion formulation (LEM) increases the bioavailability of EPA/DHA compared to the reference formulation (RF) in healthy volunteers. Following relative bioavailability assessment, LEM, RF, and placebo were dosed for 2 weeks. Exposure measurements included plasma-free and total fatty acid (EPA/DHA) concentrations and phospholipid and red blood cell (RBC) incorporation. Following single doses, the dose-normalized EPA plasma-corrected AUCs were 14-fold (total) and 12-fold (free) higher and DHA plasma-corrected AUCs were 10-fold (total) and 13-fold (free) higher for LEM compared to RF. EPA and DHA incorporation into phospholipids increased for all active treatments; the increase was dose dependent for EPA. An 8-fold increase over baseline was observed in EPA incorporation for LEM (4-capsule dose) compared to a 4-fold increase for RF 4 g. DHA incorporation increased to a lesser degree, and RBC incorporation also increased. Pharmacodynamic evaluations revealed slight decreases (-8% to -25%) in the mean fasting triglyceride concentrations in all groups, including placebo, compared to baseline. Following a high-fat meal, no consistent treatment-related effect on the triglyceride profiles was observed. Study treatments were safe and tolerated. In conclusion, LEM improves the oral bioavailability of EPA and DHA.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Hussey
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Samm
authors.initials: S
authors.lastname: Portelli
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fossler
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Harris
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Blum
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Lates
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gould
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Abu-Baker
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Johnson
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, and Philadelphia, PA, USAOmegaQuant, LLC, Sioux Falls, SD, USABuffalo Clinical Research Center, LLC, Buffalo, NY, USA.
authors.forename: Karunakar K
authors.initials: KK
authors.lastname: Reddy
keywords: DHA; EPA; emulsions; omega‐3‐acid ethyl esters; pharmacokinetics