A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study

J Clin Lipidol. 2012 Nov-Dec;6(6):573-84. doi: 10.1016/j.jacl.2012.01.002. Epub 2012 Jan 24.


Background: Omega-3 (OM-3) fatty acid products are indicated for the treatment of severe hypertriglyceridemia; however, the omega-3-acid ethyl ester (OM-3 EE) formulations require significant pancreatic lipase stimulation with high-fat meals for adequate intestinal absorption of the metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A novel omega-3 free fatty acid (OM-3 FFA) formulation (Epanova(®), Omthera Pharmaceuticals Inc., Princeton, NJ) was developed to maximize EPA and DHA bioavailability during a low-fat diet.

Objective: To compare the relative bioavailability of EPA and DHA from single 4-gram doses of OM-3 FFA and a prescription OM-3 EE (Lovaza(®), GlaxoSmithKline, Research Triangle Park, NC).

Methods: This was a randomized, open-label, single dose, 4-way crossover, bioavailability study of OM-3 FFA and OM-3 EE administered during periods of low-fat and high-fat consumption to 54 overweight adults. Bioavailability was determined by the ln-transformed area under the plasma concentration versus time curve (AUC(0-t)) during a 24-hour interval for EPA and DHA (baseline-adjusted).

Results: The baseline-adjusted AUC(0-t) for total EPA + DHA during the low-fat period was 4.0-fold greater with OM-3 FFA compared with OM-3 EE (2650.2 vs 662.0 nmol·h/mL, respectively; P < .0001). During the high-fat period, AUC(0-t) for OM-3 FFA was approximately 1.3-fold greater than OM-3 EE (P < .0001). During the low-fat period, 30 of 51 (58.8%) subjects dosed with OM-3 FFA maintained an AUC(0-t) that was ≥50% of the respective high-fat AUC(0-t) in contrast to only 3 of 50 (6.0%) subjects dosed with OM-3 EE.

Conclusions: During a low-fat consumption period, the OM-3 FFA formulation provided dramatically improved bioavailability over the OM-3 EE formulation in overweight subjects. These findings offer a potential therapeutic advantage of the OM-3 FFA formulation for the treatment of severe hypertriglyceridemia as these patients are expected to adhere to a low-fat diet.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Diet, Fat-Restricted*
  • Diet, High-Fat / adverse effects
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / pharmacokinetics*
  • Drug Combinations
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / pharmacokinetics*
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / pharmacokinetics*
  • Female
  • Humans
  • Hypertriglyceridemia / drug therapy
  • Male
  • Middle Aged
  • Molecular Structure
  • Overweight / drug therapy
  • Prospective Studies
  • Time Factors
  • Young Adult


  • Drug Combinations
  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Omacor