RT Journal Article
SR Electronic
T1 EFFECT OF MILK THISTLE (<em>SILYBUM MARIANUM</em>) AND BLACK COHOSH (<em>CIMICIFUGA RACEMOSA</em>) SUPPLEMENTATION ON DIGOXIN PHARMACOKINETICS IN HUMANS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 69
OP 74
DO 10.1124/dmd.105.006312
VO 34
IS 1
A1 Bill J. Gurley
A1 Gary W. Barone
A1 D. Keith Williams
A1 Julie Carrier
A1 Philip Breen
A1 C. Ryan Yates
A1 Peng-fei Song
A1 Martha A. Hubbard
A1 Yudong Tong
A1 Sreekhar Cheboyina
YR 2006
UL http://dmd.aspetjournals.org/content/34/1/69.abstract
AB Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may underlie many herb-drug interactions. Serial serum concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo. Sixteen healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg daily) or black cohosh (40 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 (Lanoxicaps, 0.4 mg) was administered orally before and at the end of each supplementation and control period. Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the serum concentration time curves from 0 to 3 h (AUC(0–3)), AUC(0–24), Cmax, apparent oral clearance of digoxin (CL/F), and elimination half-life were used to assess the effects of milk thistle, black cohosh, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p &lt; 0.01) in AUC(0–3), AUC(0–24), and Cmax, whereas clarithromycin increased these parameters significantly (p &lt; 0.01). Significant changes in digoxin half-life and CL/F were also observed with clarithromycin. No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh, although digoxin AUC(0–3) and AUC(0–24) approached significance (p = 0.06) following milk thistle administration. When compared with rifampin and clarithromycin, supplementation with these specific formulations of milk thistle or black cohosh 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