Permeability studies of Kavalactones using a Caco‐2 cell monolayer model

Summary Objective:  To examine the bioavailability of kavalactones in vitro and the possible differences in their bioavailability because of variations in either chemical structure or the method of extraction used. Research design and methods:  Caco‐2 cell monolayers were used to determine the potential bioavailability of kavalactones. Kavalactones were added to the apical layer and basolateral samples were taken over 150 min to examine the concentration diffusing across the cell monolayer. Kavalactone concentrations in these samples were determined by high pressure liquid chromatography. Results:  Kavalactones were found to be potentially bioavailable as they all readily crossed the Caco‐2 monolayers with apparent permeabilities ( P app ) increasing from 42 × 10 −6  cm/s and most exhibiting more than 70% crossing within 90 min. Not all differences in their bioavailability can be related to kavalactone structural differences as it appears that bioavailability may also be affected by co‐extracted compounds. For example, the P app for kawain from ethanol extracts was higher than the values obtained for the same compound from water extracts or for the kavalactone alone. Conclusions:  While the extraction method used (ethanol or water) influences the total (but not the relative) concentrations of kavalactones, it does not markedly affect their bioavailability. Hence, any differences between an ethanolic or an aqueous extract in terms of the propensity of kava to cause liver damage is not because of differing kavalactone bioavailabilities.