RT Journal Article SR Electronic T1 EXTRACTS AND KAVALACTONES OF PIPER METHYSTICUM G. FORST (KAVA-KAVA) INHIBIT P-GLYCOPROTEIN IN VITRO JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1580 OP 1583 DO 10.1124/dmd.105.005892 VO 33 IS 11 A1 Johanna Weiss A1 Alexandra Sauer A1 Andreas Frank A1 Matthias Unger YR 2005 UL http://dmd.aspetjournals.org/content/33/11/1580.abstract AB Root extracts from kava-kava (Piper methysticum G. Forst) are clinically used for the treatment of anxiety and restlessness. Due to reported cases of liver toxicity, kava-kava extracts were withdrawn from the market in several countries in 2002. Because the efflux transporter P-glycoprotein (P-gp) is involved in the absorption, distribution, and excretion of many drugs and often participates in drug-drug interactions, we studied the effect of a crude kava extract and the main kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin on the P-gp-mediated efflux of calcein-acetoxymethylester in the P-gp-overexpressing cell line P388/dx and the corresponding cell line P388. The crude extract and the kavalactones showed a moderate to potent inhibitory activity with f2 (concentration needed to double baseline fluorescence) values of 170 μg/ml and 17 to 90 μM, respectively. The f2 value of yangonin could not be determined due to its higher lipophilicity. In conclusion, our results for the first time demonstrate P-gp-inhibitory activity of kava-kava and its components in vitro. The American Society for Pharmacology and Experimental Therapeutics