Effect of goldenseal, black cohosh, kava kava, and valerian on human cytochrome p450 1A2, 2D6, 2E1, and 3A4 phenotypes

Abstract

Background Phytochemical-mediated modulation of cytochrome P450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine whether supplementation of goldenseal, black cohosh, kava, or valerian extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods Twelve healthy volunteers were randomly assigned to receive each supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hr), paraxanthine/caffeine serum ratios (6-hr), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hr), and debrisoquine urinary recovery ratios (8-hr), respectively. Results Comparisons of pre- and post-goldenseal phenotypic ratios revealed significant inhibition (~40%) of CYP2D6 and CYP3A4 activity. Black cohosh also inhibited CYP2D6, but the magnitude (~7%) did not appear clinically relevant. No significant changes were observed for kava or valerian. Conclusions Goldenseal strongly inhibited CYP2D6 and CYP3A4 activity. Accordingly, serious adverse interactions may result if goldenseal is ingested with drugs that are CYP2D6 and CYP3A4 substrates. Kava, black cohosh and valerian appear less likely to produce such interactions. Clinical Pharmacology & Therapeutics (2005) 77, P36–P36; doi: 10.1016/j.clpt.2004.12.030