Skip to main content

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

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.

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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

Author information

Affiliations

Authors

Corresponding author

Correspondence to Rudolf Bauer.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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, A36 (2009). https://doi.org/10.1186/1471-2210-9-S2-A36

Download citation

Keywords

  • Mean Residence Time
  • Relative Bioavailability
  • Pharmacological Testing
  • Plant Constituent
  • Echinacea Purpurea
\