Assessment of milk thistle and black cohosh supplementation on digoxin pharmacokinetics

Abstract

Background Phytochemical-mediated modulation of p-glycoprotein (P-gp) and other drug transporters may underlie many herb-drug interactions. Serial plasma concentration-time profiles of digoxin (DIG) (a P-gp substrate) were used to determine whether supplementation with milk thistle (MT) or black cohosh (BC) modulated P-gp activity in vivo. Methods Sixteen healthy volunteers were randomly assigned to receive each supplement, on separate occasions, for 14 days followed by a 30-day washout period. Subjects were also randomized to receive rifampin (RIF) (600 mg daily for 7 days) and clarithromycin (CLT) (1000 mg daily for 7 days) as positive controls for P-gp induction and inhibition, respectively. DIG (Lanoxicaps, 0.4 mg) was administered orally before and at the end of each supplementation and control period. Serial DIG plasma concentrations were obtained over 24 hours. Comparisons of AUC, Cmax, and Tmax were used to assess the effects of MT, BC, RIF, and CLT on DIG pharmacokinetics. Results RIF produced significant reductions (p<0.01) in AUC and Cmax, while CLT increased these parameters significantly (p<0.01). No statistically significant effects on DIG pharmacokinetics were observed following supplementation with either MT or BC, although BC approached significance for AUC (p= 0.05). Conclusions When compared to RIF and CLT, supplementation with MT or BC did not appear to affect DIG pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. Clinical Pharmacology & Therapeutics (2005) 77, P49–P49; doi: 10.1016/j.clpt.2004.12.078