Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo.

B J Gurley, A Swain, M A Hubbard, F Hartsfield, J Thaden, D K Williams, W B Gentry, Y Tong

Journal: Clinical pharmacology and therapeutics 2008;83(1):61-9

PMID: 17495878

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Abstract

The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on human CYP3A activity were evaluated using midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly assigned to receive either goldenseal or kava kava for 14 days. Each supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os) was administered before and after each phase, and pharmacokinetic parameters were determined using standard non-compartmental methods. Comparisons of pre- and post-supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal (AUC(0-infinity), 107.9+/-43.3 vs 175.3+/-74.8 ng x h/ml; Cl/F/kg, 1.26+/-0.59 vs 0.81+/-0.45 l/h/kg; T(1/2), 2.01+/-0.42 vs 3.15+/-1.12 h; Cmax, 50.6+/-26.9 vs 71.2+/-50.5 ng/ml). MDZ disposition was not affected by kava kava supplementation. These findings suggest that significant herb-drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates.

Address: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. [email protected]

DOI: 10.1038/sj.clpt.6100222

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MeSH Terms: Adult, Clarithromycin, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Enzyme System, Dietary Supplements, Enzyme Induction, Enzyme Inhibitors, Female, Herb-Drug Interactions, Humans, Hydrastis, Kava, Male, Midazolam, Models, Biological, Phenotype, Plant Preparations, Rifampin, Risk Assessment, Substrate Specificity