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


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.


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.


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%.


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.


  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.

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

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Correspondence to Rudolf Bauer.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Wölkart, K., Frye, R., Derendorf, H. et al. Absolute and relative bioavailabilities of dodeca-2E, 4E, 8E, 10E/Z-tetraenoic acid isobutylamides after intravenous and oral single doses in rats. BMC Pharmacol 9 (Suppl 2), A36 (2009).

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