Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study
Received 25 June 2013
Accepted for publication 19 August 2013
Published 1 October 2013 Volume 2013:9 Pages 563—573
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Elliot Offman,1 Ted Marenco,1 Sandy Ferber,2 Judith Johnson,3 Douglas Kling,3 Danielle Curcio,3 Michael Davidson3
1Clinical Pharmacology Sciences, Celerion, Montreal, QC, Canada; 2Array Biostatistics LLC, Evanston, IL, USA; 3Omthera Pharmaceuticals Inc, Princeton, NJ, USA
Abstract: The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is dependent on the presence of intestinal lipases and is highest during consumption of high-fat meals. Given that patients with cardiovascular disease are advised to reduce dietary fat intake, potentially lowering the bioavailability and therapeutic benefit, the hypothesis that FFA forms provide for higher bioavailability compared with EE forms under low-fat diet conditions was tested where the pharmacokinetics of the FFA form (Epanova™) were compared with those of an ethyl ester form (Lovaza®) following repeat dosing. Fifty-two healthy male and female subjects were equally allocated to one of two open-label, parallel-group cohorts. Following a Therapeutic Lifestyle Changes diet for a minimum of 7 days, blood samples were drawn for endogenous values for EPA and DHA over a 24-hour period. Subjects were then administered 4 × 1 g capsules of either Epanova (OM3 FFA) or Lovaza (OM3 EE) once daily for 14 days, following which serial blood samples were drawn over a 24-hour period to characterize the bioavailability of EPA and DHA from the respective formulations. In addition, changes from baseline in lipid profile were explored. Systemic bioavailability, as measured by area under the curve from time zero to 24 hours (AUC0–τ) and the maximum measured plasma concentrations during the 0–24 hour dosing interval (Cmax,ss) of unadjusted total plasma EPA + DHA were approximately 3-fold and 3.9-fold higher, respectively, for Epanova relative to Lovaza. Following baseline adjustment, the magnitude of difference in bioavailability was approximately 5.8-fold and 6.5-fold higher in AUC0–τ and Cmax,ss, respectively, for Epanova relative to Lovaza. Serum triglycerides were reduced by a significantly greater extent (P = 0.013) for Epanova relative to Lovaza (21% versus 8%). The bioavailability of the FFA forms of EPA and DHA in Epanova are significantly greater than the bioavailability from the EE forms present in Lovaza under low-fat dietary conditions normally recommended for patients with cardiovascular disease. This increased bioavailability may lead to improved triglyceride-lowering in patients with hypertriglyceridemia.
Keywords: hypertriglyceridemia, eicosapentaenoic acid, docosahexaenoic acid, pharmacokinetics
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