title: 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.
abstract: 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.
authors: Omthera Pharmaceuticals, Inc., Princeton, NJ 08540, USA. mdavidson@omthera.com
authors: Michael H
authors: MH
authors: Davidson
authors: Judith
authors: J
authors: Johnson
authors: Michael W
authors: MW
authors: Rooney
authors: Michael L
authors: ML
authors: Kyle
authors: Douglas F
authors: DF
authors: Kling
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D050177:Overweight / Q000188:drug therapy; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor