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

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, 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.

The bioavailability of an omega‐3‐rich algal oil is improved by nanoemulsion technology using yogurt as a food vehicle

“…The Food & Drug Administration (2003) defines bioavailability as 'the rate and extent to which the active ingredient (in this case omega-3) is absorbed and becomes available at the site of action' (FDA, 2003). Previous studies have shown that the absorption of free fatty acids from eicosapentaenoic acid (EPA) and DHA depends largely on the presence of intestinal lipases and is generally highest during the consumption of high-fat meals (Offman et al, 2013). Work by the same authors has also shown that higher absorption rates are reflected by increases in blood EPA and DHA levels [demonstrated using area under the curve (AUC) calculations], with study findings showing that the bioavailability of free fatty acid forms of EPA and DHA was significantly higher than the bioavailability from ethyl ester forms, even under low-fat conditions (Offman et al, 2013).…”

Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia

“…The ECLIPSE II trial also showed significantly greater serum levels of EPA and DHA for those on OM3-CA compared to OM3-EE while on a low-fat diet, however, after a longer time period of 14 days (Figure 1). 41 Furthermore, OM3-CA was more effective than OM3-EE at lowering TG levels (21% vs 8%, p =0.013) at 14 days. This suggests that a greater magnitude of benefit can be expected from OM3-CA compared to older OM3-FA formulations.…”

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs

“…In this study, non-HDL-C, TC/non-HDL-C, VLDL, remnant-like particle cholesterol, apoC-III, Lp-PLA 2 , and arachidonic acid (AA) levels were significantly lowered as compared with placebo, but LDL-C was also substantially increased. One advantage is that the availability of the FFA form is up to fourfold higher than from the EE form under low-fat dietary conditions [155][156][157]. In the Epanova combined with a Statin in Patients with hypeRglyerIdemia to reduce non-HDL cholesTerol (ESPRIT) trial, FFA omega-3 was administered to high-risk patients taking statins with TGs between 2.26 and 5.63 mmol/L (200-499 mg/dL); a dose of 2 g/day was found to be effective and well-tolerated for lowering non-HDL-C and TGs, as opposed to a higher dose of 4 g/day of other forms [157].…”