Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans

Bill J. Gurley, Ashley Swain, Gary W. Barone, D. Keith Williams, Philip Breen, Charles Yates, Leslie B. Stuart, Martha A. Hubbard, Yudong Tong, Sreekhar Cheboyina

Research output: Contribution to journalArticle

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Abstract

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, t1/2, and C max, whereas clarithromycin increased these parameters significantly (p < 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.

Original languageEnglish (US)
Pages (from-to)240-245
Number of pages6
JournalDrug Metabolism and Disposition
Volume35
Issue number2
DOIs
StatePublished - Feb 1 2007

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Hydrastis
Kava
Digoxin
Pharmacokinetics
P-Glycoprotein
Clarithromycin
Rifampin
Area Under Curve
Herb-Drug Interactions
Phytochemicals
Immunoassay
Half-Life
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. / Gurley, Bill J.; Swain, Ashley; Barone, Gary W.; Williams, D. Keith; Breen, Philip; Yates, Charles; Stuart, Leslie B.; Hubbard, Martha A.; Tong, Yudong; Cheboyina, Sreekhar.

In: Drug Metabolism and Disposition, Vol. 35, No. 2, 01.02.2007, p. 240-245.

Research output: Contribution to journalArticle

Gurley, BJ, Swain, A, Barone, GW, Williams, DK, Breen, P, Yates, C, Stuart, LB, Hubbard, MA, Tong, Y & Cheboyina, S 2007, 'Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans', Drug Metabolism and Disposition, vol. 35, no. 2, pp. 240-245. https://doi.org/10.1124/dmd.106.012708
Gurley, Bill J. ; Swain, Ashley ; Barone, Gary W. ; Williams, D. Keith ; Breen, Philip ; Yates, Charles ; Stuart, Leslie B. ; Hubbard, Martha A. ; Tong, Yudong ; Cheboyina, Sreekhar. / Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. In: Drug Metabolism and Disposition. 2007 ; Vol. 35, No. 2. pp. 240-245.
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