Planta Med 2009; 75(12): 1306-1313
DOI: 10.1055/s-0029-1185631
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics and Tissue Distribution of Dodeca-2E,4E,8E,10E/Z-tetraenoic Acid Isobutylamides after Oral Administration in Rats

Karin Woelkart1 , 3 , Reginald F. Frye2 , Hartmut Derendorf1 , Rudolf Bauer3 , Veronika Butterweck1
  • 1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA
  • 2Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville, Florida, USA
  • 3Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Graz, Austria
Further Information

Publication History

received Dec. 13, 2008 revised March 15, 2009

accepted March 19, 2009

Publication Date:
27 April 2009 (online)

Abstract

The present study investigated the pharmacokinetics and tissue distribution of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (tetraenes), the main alkamides in Echinacea preparations, in rats after a single oral dose administration of 2.5 mg/kg. Plasma, liver and 4 different brain regions (hippocampus, cerebral cortex, striatum and cerebellum) were collected after 8, 15, 30 minutes and 1, 2, 3 and 6 hours after oral dosing. Plasma and tissue concentrations were determined by a rapid (5 min) liquid chromatography-tandem mass spectrometry (LC‐MS/MS) method with benzanilide as internal standard (IS) using the respective [M – H]+ ions, m/z = 248/152 for the dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides and m/z = 198/105 for the IS. The lipophilic constituents were rapidly absorbed, with a Tmax of 15 minutes, distributed and appeared in the brain already within 8 minutes. The total amount of tetraenes in different brain parts was calculated as AUC0-∞ (range: 1764–6192 min × ng/g) and compared to the concentrations found in plasma (794 min × ng/mL) and liver tissues (1254 min × ng/g). The Cmax in plasma was 26.4 ng/mL, while the Cmax in the different brain regions varied between 33.8 ng/g and 46.0 ng/g. In the striatum the highest concentration and the longest elimination half-life of 253 minutes with a mean residence time of 323 minutes was detected. The results demonstrate that the dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides are bioavailable in rats with a rapid passage across the blood-brain barrier.

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Dr. Veronika Butterweck

Department of Pharmaceutics
College of Pharmacy, University of Florida

1600 SW Archer Road

Gainesville, FL 32610

USA

Phone: + 1 35 22 73 78 59

Fax: + 1 35 22 73 78 54

Email: butterwk@cop.ufl.edu