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

Elizabeth K. Hussey, Samm Portelli, Michael J. Fossler, Feng Gao, William Harris, Robert A. Blum, Christian D. Lates, Elizabeth Gould, Omar Abu-Baker, Susan Johnson, Karunakar K. Reddy

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
JournalClinical Pharmacology in Drug Development
Volume1
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Eicosapentaenoic Acid
Docosahexaenoic Acids
Emulsions
Biological Availability
Healthy Volunteers
Esters
Acids
Triglycerides
Area Under Curve
Phospholipids
Erythrocytes
Placebos
Nonesterified Fatty Acids
Capsules
Meals
Fasting
Therapeutics
Fats
Diet

Keywords

  • DHA
  • emulsions
  • EPA
  • omega-3-acid ethyl esters
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmaceutical Science

Cite this

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. / Hussey, Elizabeth K.; Portelli, Samm; Fossler, Michael J.; Gao, Feng; Harris, William; Blum, Robert A.; Lates, Christian D.; Gould, Elizabeth; Abu-Baker, Omar; Johnson, Susan; Reddy, Karunakar K.

In: Clinical Pharmacology in Drug Development, Vol. 1, No. 1, 01.2012, p. 14-23.

Research output: Contribution to journalArticle

Hussey, Elizabeth K. ; Portelli, Samm ; Fossler, Michael J. ; Gao, Feng ; Harris, William ; Blum, Robert A. ; Lates, Christian D. ; Gould, Elizabeth ; Abu-Baker, Omar ; Johnson, Susan ; Reddy, Karunakar K. / 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. In: Clinical Pharmacology in Drug Development. 2012 ; Vol. 1, No. 1. pp. 14-23.
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