ASsessment of botanical supplementation on human cytochrome P450 phenotype: citrus aurantium, echinacea, milk thistle, saw palmetto.

Abstract

Objectives Phytochemical-mediated modulation of cytochrome P-450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine if supplementation with citrus aurantium, echinacea, milk thistle, or saw palmetto affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods Twelve healthy volunteers were randomly assigned to receive each supplement for 28 days. A 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquine were administered before and at the end of each supplementation period. Pre- and post-supplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour), and debrisoquine urinary recovery ratios (8-hour collection), respectively. Phytochemical content was determined for each supplement. Results Comparisons of pre- and post-supplementation phenotypic ratios indicated that these particular supplements had no significant effect on CYP activity. Citrus aurantium was devoid of the CYP3A4 inhibitor, 6,7-dihydroxybergamottin. Conclusions Botanical supplements containing citrus aurantium, echinacea, milk thistle, or saw palmetto appear to pose a minimal risk for CYP-mediated herb-drug interactions in humans. Clinical Pharmacology & Therapeutics (2004) 75, P35–P35; doi: 10.1016/j.clpt.2003.11.134