Bioequivalence of two omega-3 fatty acid ethyl ester formulations: a case of clinical pharmacology of dietary supplements

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Omega-3 fatty acids are dietary components, present in the body with variable blood levels. • Bioavailability evaluations of ethyl ester preparations are hampered by the difficulty in achieving similar concentrations of EPA and DHA in the preparations being compared. This may require questionable corrections for baseline concentrations. • If repeated doses are given, this may lead to errors because of variable dietary fish intake. If a single dose is selected, this needs to be large, since omega-3 are present in many compartments. WHAT THIS STUDY ADDS • We selected subjects with uniform omega-3 background levels, to obtain comparable results at the end of treatment. • Testing bioequivalence of two formulations with different EPA/DHA ratios led to single dose intakes of 12 g, proving to be well tolerated. • In spite of clear differences in EPA/DHA ratios between the two preparations, plasma ratios did not differ and bioequivalence could be well ascertained. AIM To evaluate the bioequivalence of two n-3 LC-PUFA ethyl ester preparations, previously shown not be bioequivalent in healthy subjects, with the objective of providing a guideline for future work in this area. METHODS A randomized double blind crossover protocol was chosen; volunteers were selected with the lowest blood levels of n-3 LC-PUFA among candidates. They received the ethyl esters in a single high dose (12 g) and EPA and DHA blood levels were analyzed after fingerprick collection at intervals up to 24 hours. RESULTS Differently from a prior study, the pharmacokinetic analysis indicated a satisfactory bioequivalence: for the AUC0-24 90% CI of the ratio between the two formulations are in the range for bioequivalence (for EPA 0.98 – 1.04 and for DHA 0.99 – 1.04), same for Cmax and Tmax (90% CI are 0.95-1.14; 1.10-1.25 for both EPA and 0.88-1.02; 0.84-1.24 for DHA). CONCLUSIONS This study shows that, in order to obtain reliable bioequivalence data of products present in the daily diet, certain conditions should be met. Subjects should have low, homogeneous baseline levels and not be exposed to food items containing the product under evaluation, eg fish. Finally, as in the case of Omega-3 FA, selected doses should be high, eventually with appropriate conditions of intake.