PT - JOURNAL ARTICLE AU - Bill J. Gurley AU - Ashley Swain AU - Gary W. Barone AU - D. Keith Williams AU - Philip Breen AU - C. Ryan Yates AU - Leslie B. Stuart AU - Martha A. Hubbard AU - Yudong Tong AU - Sreekhar Cheboyina TI - Effect of Goldenseal (<em>Hydrastis canadensis</em>) and Kava Kava (<em>Piper methysticum</em>) Supplementation on Digoxin Pharmacokinetics in Humans AID - 10.1124/dmd.106.012708 DP - 2007 Feb 01 TA - Drug Metabolism and Disposition PG - 240--245 VI - 35 IP - 2 4099 - http://dmd.aspetjournals.org/content/35/2/240.short 4100 - http://dmd.aspetjournals.org/content/35/2/240.full SO - Drug Metab Dispos2007 Feb 01; 35 AB - Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)(0–3), AUC(0–24), Cmax, CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p &lt; 0.01) in AUC(0–3), AUC(0–24), CL/F, t1/2, and Cmax, whereas clarithromycin increased these parameters significantly (p &lt; 0.01). With the exception of goldenseal's effect on Cmax (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. The American Society for Pharmacology and Experimental Therapeutics