title: Bioequivalence of two omega-3 fatty acid ethyl ester formulations: a case of clinical pharmacology of dietary supplements.
abstract: BACKGROUND
  • Omega-3 fatty acids are dietary components, present in the body with variable blood concentrations. • Bioavailability evaluations of ethyl ester preparations are hampered by the difficulty in achieving similar concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (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 LC-PUFA are present in many compartments.
  
  
  CONCLUSIONS
  • We selected subjects with uniform omega-3 background concentrations, 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, which were 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.
  
  
  OBJECTIVE
  To evaluate the bioequivalence of two omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) ethyl ester preparations, previously shown not to 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 with the lowest blood concentrations of n-3 LC-PUFA were selected. They received the ethyl esters in a single high dose (12 g) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blood concentrations were analyzed after fingerprick collection at intervals up to 24 h.
  
  
  RESULTS
  Differently from a prior study, the pharmacokinetic analysis indicated a satisfactory bioequivalence: for the AUC(0,24 h) 90% CI of the ratio between the two formulations were in the range for bioequivalence (for EPA 0.98, 1.04 and for DHA 0.99, 1.04) and the same was true for C(max) and t(max) (90% CI were 0.95, 1.14 and 1.10, 1.25 for EPA and 0.88, 1.02 and 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 concentrations and not be exposed to food items containing the product under evaluation, e.g. fish. Finally, as in the case of omega-3 fatty acids, selected doses should be high, eventually with appropriate conditions of intake.
authors.affiliation: Department of Pharmacological Sciences, Università di Milano, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Galli
authors.forename: Franco M
authors.initials: FM
authors.lastname: Maggi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Risé
authors.forename: Cesare R
authors.initials: CR
authors.lastname: Sirtori
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid