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

Abstract

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, 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.

Toxicity of Kava Kava

“…Gurley et al (86) found that kava is not a potent modulator of P-gp in humans. The inducible transcription factor nuclear, factor kappaB (NFkappaB), regulates immune, inflammatory, and carcinogenic responses.…”

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

“…Ranunculaceae) has a history of folk medicine use in the treatment of gastrointestinal disturbances, urinary disorders, skin ailments and various infections [2,4]. A clinical trial showed that goldenseal did not change the disposition of digoxin, suggesting that this herb has no effect on P-glycoprotein [105]. Although one study did not yield the same conclusions [106], convincing clinical evidence suggests that adverse herb-to-drug interactions may result with concomitant ingestion of goldenseal and drugs that are metabolized by CYP3A4 or CYP2D6 [14,17,107,108].…”

Hydrastine Pharmacokinetics and Metabolism after a Single Oral Dose of Goldenseal (Hydrastis canadensis) to Humans

“…Goldenseal supplement was purchased from Nature's Resource (Lot #0/10184; Mission Hills, CA). This brand of Goldenseal was chosen because it was used in previous human studies conducted by our group (Gurley et al, 2007(Gurley et al, , 2008bGupta et al, 2009) and the manufacturer (Pharmavite, LLC) claims to follow current good manufacturing practices in the sourcing and manufacture of its products. Each goldenseal was independently determined to contain 13 mg of hydrastine.…”