Pharmacokinetics of the Main Alkamides after Administration of three Different Echinacea purpurea Preparations in Humans

Abstract

Establishing the pharmacological basis for efficacy of herbal medicinal products (HMPs) is a continuous challenge. In this context, also the question of bioavailability, the elucidation of metabolic pathways and their pharmacokinetics is of major interest. These data are relevant to link results from pharmacological in vitro assays and clinical studies. A better understanding of the pharmacokinetics and bioavailability of phytopharmaceuticals can also help in designing rational dosage regimes. The preparations used in the present pharmacokinetic single-dose study are different Echinacea purpurea formulations (Echinaforce^TM) with various excipients. The concentrations of the active compounds (alkamides) in the administered products have been in the low mg range per dose. Due to the expected necessary detection of ng ranges, a sensitive and selective LC-ESI-MS-based method that is capable of monitoring plasma levels of traces of active constituents in humans was developed and validated. The resulting maximum concentrations (mean ± standard deviation) of dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides in plasma were 0.22 ± 0.07 ng/mL after administration of Echinaforce^TM tablets, 0.22 ± 0.15 ng/mL after taking Echinaforce Junior tablets and 0.23 ± 0.16 ng/mL after administration of an Echinacea sore throat spray. The areas under the curve were 0.22 ng/mL × h, 0.20 ng/mL × h and 0.23 ng/mL × h, respectively.

Key words

Echinacea purpurea - alkamides - pharmacokinetics - humans - Asteraceae

References

• 1 Felter H W, Lloyd J U. Echinacea. - Echinacea. In: Felter HW, Lloyd JU, editors King’s American Dispensatory, 18th edition, 3 rd revision. First published 1905. reprinted Portland; Eclectic Medical Publications 1983: 671-7
• 2 Barrett B. Medicinal properties of Echinacea : a critical review.  Phytomedicine. 2003;  10 66-86
• 3 Barnes J, Anderson L A, Gibbons S, Phillipson J D. Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): A review of their chemistry, pharmacology and clinical properties.  J Pharm Pharmacol. 2005;  57 929-54
• 4 Gertsch J, Schoop R, Kuenzle U, Suter A. Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB₂ and multiple signal transduction pathways.  FEBS Lett. 2004;  577 563-9
• 5 Woelkart K, Marth E, Raggam R, Suter A, Schoop R, Koidl C. et al . Bioavailability and pharmacokinetic studies on Echinacea purpurea preparations and their interaction with the immune system.  Int J Clin Pharm Ther . 2006;  44 01-8
• 6 Raduner S, Majewska A, Chen J -Z, Xie X -Q, Hamon J, Faller B. et al . Alkylamides from Echinacea are a new class of cannabinomimetics - CB₂-Receptor dependent and independent immunomodulatory effects.  J Biol Chem. 2006;  281 14 192-206
• 7 Bauer R, Jurcic K, Puhlmann J, Wagner H. Immunologische in vivo- und in vitro-Untersuchungen mit Echinacea Extrakten [Immunological studies in vivo and in vitro of Echinacea extracts. [Translated by Beate V.  Foit, Santa Cruz, CA] Arzneimittelforschung/Drug Res. 1988;  38 276-81
• 8 Bauer R, Remiger P, Jurcic K, Wagner H. Beeinflussung der Phagozytose-Aktivität durch Echinacea-Extrakte [Influence of Echinacea extract on phagocytotic activity. [Reviewed in translation, translator unknown].  Z Phytother. 1989;  10 3-8
• 9 Rininger J A, Kickner S, Chigurupati P, McLean A, Franck Z. Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells.  J Leukoc Biol. 2000;  68 503-10
• 10 Blumenthal M. The complete German Commission E monographs, therapeutic guide to herbal medicines. Austin; American Botanical Council; Boston: Integrative Medicine Communications 1998
• 11 Woelkart K, Koidl C, Grisold A, Gangemi J D, Turner R B, Marth E. et al . Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans.  J Clin Pharmacol. 2005;  45 683-9
• 12 Jager H, Meinel L, Dietz B, Lapke C, Bauer R, Merkle H P. et al . Transport of alkamides from Echinacea species through Caco-2 monolayers.  Planta Med. 2002;  68 469-71
• 13 Matthias A, Blanchfield J T, Penman K G, Toth I, Lang C -S, De Voss J J. et al . Permeability studies of alkylamides and caffeic acid conjugates from Echinacea using Caco-2 cell monolayer model.  J Clin Pharm Ther. 2004;  29 7-13
• 14 Woelkart K, Bauer R. The role of alkamides as an active principle of Echinacea. .  Planta Med. 2007;  73 1-9