title: Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. gurleybillyj@uams.edu
authors.forename: B J
authors.initials: BJ
authors.lastname: Gurley
authors.forename: A
authors.initials: A
authors.lastname: Swain
authors.forename: M A
authors.initials: MA
authors.lastname: Hubbard
authors.forename: F
authors.initials: F
authors.lastname: Hartsfield
authors.forename: J
authors.initials: J
authors.lastname: Thaden
authors.forename: D K
authors.initials: DK
authors.lastname: Williams
authors.forename: W B
authors.initials: WB
authors.lastname: Gentry
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
mesh_terms: D000328:Adult; D017291:Clarithromycin / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019587:Dietary Supplements; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D039321:Hydrastis; D020901:Kava; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D008954:Models, Biological; D010641:Phenotype; D028321:Plant Preparations / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D018570:Risk Assessment; D013379:Substrate Specificity
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017291:Clarithromycin; D008874:Midazolam; D012293:Rifampin