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Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives

To assess the comparative pharmacokinetic profile and bioavailability of docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) after multiple-dose administration of a new oral formulation (test formulation) and a commercially available reference formulation in healthy subjects.

Methods

Forty-eight healthy subjects received a 28-day oral treatment with DHA/EPA in the form of either the test or the reference product according to an open-label, randomized, parallel-group design. Both formulations were given t.i.d. at 8-h intervals at a dose of 3.0 g/day. Steady-state DHA and EPA concentrations in plasma and lysed whole blood were measured by gas-liquid chromatography at baseline and after 7, 14, 21 and 28 days of treatment. Kinetic parameters were compared both after subtraction of baseline concentrations and by using baseline concentrations as a covariate.

Results

For both DHA and EPA, plasma and RBC concentrations measured from day 7 to day 28 were significantly higher than at baseline and did not differ significantly between the two products. On day 28 the plasma DHA concentration on average doubled the baseline level after administration of test and reference product, while there was a 10-fold increase in EPA plasma concentration. When the assessment was performed using baseline values as covariate, test-to-reference ratios for area under the curve (AUCss0–8) and for peak concentration (Cssmax) after the last administration on day 28 met bioequivalence criteria (i.e., 90% confidence intervals within 0.80–1.25 for AUCss0–8 ratios, and within 0.75–1.33 for Cssmax ratios). When the assessment was conducted after subtraction of baseline values, the 90% confidence intervals for Cssmax ratios were within the bioequivalence range, whereas the intervals for AUCss0–8 ratio were borderline for bioequivalence.

Conclusion

The two formulations tested were similarly effective in increasing DHA and EPA concentrations in plasma and lysed whole blood, and showed comparable bioavailability for both active components.

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Acknowledgements

IBSA Institut Biochimique SA, Switzerland, provided the study medication. The relationships between the sponsor and the institutions of AR, ADS and MVD were regulated by financial agreements. CS is a full-time employee of IBSA. EP has received speaker’s or consultancy fees or research/travel grants from Cyberonics, GSK, Janssen-Cilag, Johnson & Johnson, IBSA, Novartis, Pfizer, Sanofi-Aventis, Schwartz-Pharma, SK Holdings, UCB Pharma, Valeant. All experimental procedures performed in the study were in accordance with Swiss law. No potential conflict of interest exists in relation to this article.

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Authors and Affiliations

  1. IBSA, Institut Biochimique SA, Via del Piano, P.O. Box 266, CH-6915, Pambio-Noranco, Switzerland

    Claudia Scarsi

  2. ABS Laboratories Ltd., Wardalls Grove, Avonley Road, London, SE14 5ER, UK

    Mira V. Doig

  3. Cross Research S.A., via F. A. Giorgioli, Arzo, Switzerland

    Antonio Rusca & Andrea Francesco Daniele Di Stefano

  4. Institute of Neurology, IRCCS C. Mondino Foundation and Clinical Pharmacology Unit, University of Pavia, Pavia, Italy

    Emilio Perucca

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  1. Antonio Rusca
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  2. Andrea Francesco Daniele Di Stefano
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  3. Mira V. Doig
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  4. Claudia Scarsi
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  5. Emilio Perucca
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Correspondence to Claudia Scarsi.

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Rusca, A., Di Stefano, A.F.D., Doig, M.V. et al. Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers. Eur J Clin Pharmacol 65, 503–510 (2009). https://doi.org/10.1007/s00228-008-0605-4

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  • DOI: https://doi.org/10.1007/s00228-008-0605-4

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