Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.
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.
Gurley
Bill J
BJ
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy, 4301 West Markham Street, Slot 522-3, Little Rock, AR 72205, USA. gurleybillyj@uams.edu
Swain
Ashley
A
Barone
Gary W
GW
Williams
D Keith
DK
Breen
Philip
P
Yates
C Ryan
CR
Stuart
Leslie B
LB
Hubbard
Martha A
MA
Tong
Yudong
Y
Cheboyina
Sreekhar
S
D000328:Adult; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000494:pharmacology; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D039321:Hydrastis; D020901:Kava; D008297:Male; D012293:Rifampin / Q000494:pharmacology
D002316:Cardiotonic Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004077:Digoxin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017291:Clarithromycin; D012293:Rifampin