Absolute/Relative Bioavailability and Metabolism of Dodeca-2E,4E,8Z,10E/Z-Tetraenoic Acid Isobutylamides (Tetraenes) after Intravenous and Oral Single Doses to Rats

Karin Ardjomand-Woelkart; Manfred Kollroser; Christoph Magnes; Frank Sinner; Reginald F. Frye; Hartmut Derendorf; Rudolf Bauer; Veronika Butterweck

doi:10.1055/s-0030-1271120

Planta Medica, Table of Contents

Planta Med 2011; 77(16): 1794-1799
DOI: 10.1055/s-0030-1271120

Pharmacokinetic Investigations

Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Absolute/Relative Bioavailability and Metabolism of Dodeca-2E,4E,8Z,10E/Z-Tetraenoic Acid Isobutylamides (Tetraenes) after Intravenous and Oral Single Doses to Rats

Karin Ardjomand-Woelkart¹ ^, ⁵ , Manfred Kollroser² , Christoph Magnes³ , Frank Sinner³ , Reginald F. Frye⁴ , Hartmut Derendorf¹ , Rudolf Bauer⁵ , Veronika Butterweck¹

¹Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA
²Institute of Forensic Medicine, Medical University of Graz, Graz, Austria
³Joanneum Research, Institute of Medical Technologies and Health Management, Graz, Austria
⁴Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA
⁵Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Graz, Austria

Abstract

The present study assessed the absolute and relative bioavailabilities of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (tetraenes), the main bioactive constituents in Echinacea, administered as pure compounds or in the form of an Echinacea purpurea root extract preparation. Tetraenes were administered orally by gavage or intravenously in a dose of 0.75 mg/kg. The extract was administered orally in a dose of 158.6 mg/kg which corresponds to the same amount of tetraenes. Pharmacokinetic parameters of tetraenes were calculated by non-compartmental analysis using WinNonlin® 5.2 software. Mean dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide dose-normalized plasma area under the concentration-time curve (AUC_0–∞/dose) was 3.24 ± 0.32 min · ng/mL/µg and 0.95 ± 0.16 min · ng/mL/µg after iv and oral administrations, respectively, and 1.53 ± 0.18 min · ng/mL/µg after oral administration of the Echinacea root extract. The absolute oral bioavailability of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides was 29.2 ± 2.3 %, which was increased to 47.1 ± 7.2 % (1.6-fold) by administration of the Echinacea extract. Administration of an Echinacea extract increased blood exposure with no impact on C_max, but prolonged the elimination half-life to 123.3 ± 15.7 min in comparison to 35.8 ± 6.5 min after administration of the pure dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides.

Key words

Echinacea - Asteraceae - dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides - absolute bioavailability - relative bioavailability - LC-MS

Full Text

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