QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.106.012708v2 35/2/240    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gurley, B. J. Articles by Cheboyina, S. Search for Related Content PubMed PubMed Citation Articles by Gurley, B. J. Articles by Cheboyina, S.

Effect of Goldenseal (Hydrastis canadensis) and Kava Kava (Piper methysticum) Supplementation on Digoxin Pharmacokinetics in Humans

Departments of Pharmaceutical Sciences (B.J.G., P.B., M.A.H., Y.T.), Surgery, (G.W.B.), Biometry (D.K.W.), and the General Clinical Research Center (A.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (C.R.Y., L.B.S.); and Department of Pharmaceutics, University of Mississippi, Oxford, Mississippi (S.C.)

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), C_max, 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 < 0.01) in AUC_(0–3), AUC_(0–24), CL/F, t_1/2, and C_max, whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C_max (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.

This article has been cited by other articles:

				S. S. Shord, K. Shah, and A. Lukose Drug--Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals Integr Cancer Ther, September 1, 2009; 8(3): 208 - 227. [Abstract] [PDF]