Bioavailability and Pharmacokinetics of Alkamides From the Roots of Echinacea angustifolia in Humans

Abstract

Alkamides are suspected to contribute to the activity of Echinacea preparations. They are mainly derived from undeca- and dodecanoic acid and differ in the degree of unsaturation and the configuration of the double bonds. In total, 6 alkamides have been isolated from the roots of Echinacea angustifolia as major lipophilic constituents and have been investigated regarding their pharmacokinetics. A sensitive and specific method has been developed for the identification and quantification of these alkamides in human plasma using liquid chromatography electrospray ionization ion-trap mass spectrometry. The method was applied to analyze plasma samples obtained from a randomized, open, single-dose, crossover study after oral administration of a 60% ethanolic extract from the roots of E. angustifolia to 11 healthy subjects. The maximum concentration of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, the main alkamides in the roots of E. angustifolia, appeared already after 30 minutes and was 10.88 ng/mL for the 2.5-mL dose.

Alkylamides from Echinacea Are a New Class of Cannabinomimetics

“…It was recently shown that alkylamides from Echinacea are resorbed in vivo and can be detected in nanomolar concentrations (0.5-50 nM) in human blood plasma upon ingestion (26,27).…”

“…Immunomodulatory actions of endogenous and exogenous cannabinoids have been investigated in numerous studies (18), mostly performed with isolated cells or transformed cell lines, but only sparse data exist for ex vivo studies or studies with whole blood. Recent reports have shown that plasma levels of alkylamides in the lower nanomolar range can be achieved in humans after oral administration of commercial alkylamide-containing Echinacea preparations (26,27). So far, however, it is not known whether alkylamides can exert immunomodulatory effects via the CB 2 receptor at such low concentrations.…”

Echinacea Species and Alkamides Inhibit Prostaglandin E2 Production in RAW264.7 Mouse Macrophage Cells

“…Results from a study investigating the metabolism of natural and synthetic alkylamides from Echinacea by using human liver microsomes determined that cytochrome P450 mediated epoxidation, hydroxylation, and dealkylation of alkylamides occurred (33). A recent human study analyzed 11 human subjects for bioavailability of an oral administration of a 60% ethanolic extract of E. angustifolia root, which was known to contain six identified alkamides, showing that after 30 min one of the six alkamides, dodeca-2E,4E,8Z,10E/Ztetraenoic acid isobutylamide, appeared in plasma samples at 10.88 ng/mL for a 2.5 mL dose (34). Another human study analyzed nine volunteers who consumed tablets of 675 mg of E. purpurea and 600 mg of E. angustifolia, after a high-fat breakfast or after a fast, for alkamide content in their plasma (35).…”

Effects of herbal products and their constituents on human cytochrome P4502E1 activity

“…The observed activities of all of the pretreated microsomes were identical, indicating a reversible type inhibition by the alkylamide. Several recent studies have shown that cytochrome P450 metabolizes Echinacea-derived alkylamides in vitro (Cech et al, 2006b;Woelkart et al, 2005). It has also been reported that one of the isolated alkylamides with a terminal acetylenic group appears to inhibit P450-dependent alkylamide metabolism via a mechanism-based (irreversible) process.…”