Volume 9 Supplement 2

15th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Absolute and relative bioavailabilities of dodeca-2E, 4E, 8E, 10E/Z-tetraenoic acid isobutylamides after intravenous and oral single doses in rats

  • Karin Wölkart1,
  • Reginald Frye2,
  • Hartmut Derendorf3,
  • Veronika Butterweck3 and
  • Rudolf Bauer1Email author
BMC Pharmacology20099(Suppl 2):A36

https://doi.org/10.1186/1471-2210-9-S2-A36

Published: 12 November 2009

Background

Dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides are the main alkamides in Echinacea preparations, which have been demonstrated to possess biological activities in various bio-assays, such as immune-modulating activities and effects on cannabinoid receptors [1]. Therefore, the evaluation of systemic availability of these active plant constituents is a major prerequisite for the interpretation of in vitro pharmacological testing. This study assessed the absolute and relative bioavailabilities of dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides (tetraenes) administered as pure compounds or as an Echinacea purpurea root extract preparation.

Methods

Ten rats received 0.75 mg/kg dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides orally, pure and within 158.6 mg/kg Echinacea purpurea extract, or intravenously to compare the absorption and pharmacokinetic properties. Pharmacokinetic parameters and bioavailability data of tetraenes were obtained by non-compartmental analysis (NCA) using WinNonlin® 5.2 software.

Results

Mean dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamide plasma area under the concentration-time curve (AUC0-∞ per dose) was 3.2 ± 0.3 min·ng/mL/μg and 1.0 ± 0.2 min·ng/mL/μg after i.v. and oral administration, respectively, and 1.5 ± 0.2 min·ng/mL/μg after oral administration of the Echinacea root extract. The absolute bioavailability of dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides was 29%, which was increased to 47% (1.6 fold) by the administration of an Echinacea extract. The relative bioavailability was over 100%.

Conclusion

Administration of a whole Echinacea extract increases blood exposure with no impact on Cmax. The high area under the curve concentration resulted in a longer elimination half-life with 123 min in comparison to 36 min after administration of the pure dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides. The approximately 2-fold higher percentage of relative bioavailability achieved with the Echinacea root extract resulted in a 3.4 and 3.6 times higher terminal elimination half-life and mean residence time (MRT), respectively. A rapid absorption followed by a slower elimination phase was observed.

Declarations

Acknowledgements

Supported by the Erwin-Schrödinger scholarship (FWF) J2754-B05.

Authors’ Affiliations

(1)
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl Franzens University Graz
(2)
Department of Pharmacy Practice, College of Pharmacy, University of Florida
(3)
Department of Pharmaceutics, College of Pharmacy, University of Florida

References

  1. Woelkart K, Bauer R: The role of alkamides as an active principle of Echinacea. Planta Med. 2007, 73: 615-623. 10.1055/s-2007-981531.View ArticlePubMedGoogle Scholar

Copyright

© Wölkart et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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