title: Pharmacokinetics and tissue distribution of dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides after oral administration in rats.
abstract: The present study investigated the pharmacokinetics and tissue distribution of dodeca-2 E,4 E,8 Z,10 E/ 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-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides and M/Z = 198/105 for the IS. The lipophilic constituents were rapidly absorbed, with a T (max) 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 AUC (0-infinity) (range: 1764-6192 min x ng/g) and compared to the concentrations found in plasma (794 min x ng/mL) and liver tissues (1254 min x ng/g). The C (max) in plasma was 26.4 ng/mL, while the C (max) 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-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides are bioavailable in rats with a rapid passage across the blood-brain barrier.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Woelkart
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Frye
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Veronika
authors.initials: V
authors.lastname: Butterweck
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid; D020900:Echinacea / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D013058:Mass Spectrometry; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C452804:2,4,8,10-dodecatetraenoic acid isobutylamide; D005231:Fatty Acids, Unsaturated; D053284:Polyunsaturated Alkamides