title: The free fractions of circulating docosahexaenoic acid and eicosapentenoic acid as optimal end-point of measure in bioavailability studies on n-3 fatty acids.
abstract: The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration.
authors.affiliation: IBSA Institut Biochimique SA, Via del Piano, 6915 Pambio-Noranco, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarsi
authors.affiliation: inVentiv Health Clinical, 2500 Einstein, Québec, QC, Canada G1P 0A2.
authors.forename: Ann
authors.initials: A
authors.lastname: Levesque
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, 00168 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lisi
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, 00168 Rome, Italy. Electronic address: pnavarra@rm.unicatt.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D001682:Biological Availability; D004281:Docosahexaenoic Acids / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005215:Fasting; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid
keywords: Bioavailability studies; Docosahexaenoic acid; Eicosapentenoic acid; n-3 Fatty acids