Planta Med 2009; 75 - PJ23
DOI: 10.1055/s-0029-1234828

Bioavailability of dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides after oral administration in rats and distribution in various tissues

K Woelkart 1, 3, RF Frye 2, H Derendorf 3, R Bauer 1, V Butterweck 3
  • 1Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, Universitaetsplatz 4, 8010 Graz, Austria
  • 2Department of Pharmacy Practice, College of Pharmacy, University of Florida, 1600 SW Archer Road, 32610 Gainesville, USA
  • 3Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, 32610 Gainesville, USA

The pharmacokinetics and tissue distribution of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (tetraens), the main alkamides in Echinacea preparations, were investigated in rats after a single oral dose administration of 2.5mg/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 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 and well distributed to the tissues examined. The highest concentration was found in the striatum. The total tetraens amount in plasma (794min*ng/mL) was calculated as AUC0-∞ and about 13˜45% of that found in different brain parts (1764–6192min*ng/mL), and 63% of that in liver tissues (1254min*ng/g). The Cmax in plasma was 26.4ng/mL, while the Cmax in the different brain regions varied between 33.8ng/g and 46.0ng/g.

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.

Reference: [1] Woelkart, K. et al. (2009) Planta Med. submitted.