title: Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants.
abstract: A number of herbal preparations have been shown to interact with prescription medications secondary to modulation of cytochrome P450 (CYP) and/or P-glycoprotein (P-gp). The purpose of this study was to determine the influence of Panax ginseng on CYP3A and P-gp function using the probe substrates midazolam and fexofenadine, respectively. Twelve healthy participants (8 men) completed this open-label, single-sequence pharmacokinetic study. Healthy volunteers received single oral doses of midazolam 8 mg and fexofenadine 120 mg, before and after 28 days of P ginseng 500 mg twice daily. Midazolam and fexofenadine pharmacokinetic parameter values were calculated and compared before and after P ginseng administration. Geometric mean ratios (postginseng/preginseng) for midazolam area under the concentration-time curve from zero to infinity (AUC(0-∞)), half-life (t(1/2)), and maximum concentration (C(max)) were significantly reduced at 0.66 (0.55-0.78), 0.71 (0.53-0.90), and 0.74 (0.56-0.93), respectively. Conversely, fexofenadine pharmacokinetics were unaltered by P ginseng administration. Based on these results, P ginseng appeared to induce CYP3A activity in the liver and possibly the gastrointestinal tract. Patients taking P ginseng in combination with CYP3A substrates with narrow therapeutic ranges should be monitored closely for adequate therapeutic response to the substrate medication.
authors.affiliation: Clinical Pharmacokinetics Research Laboratory, Pharmacy Department, Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Malati
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Robertson
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hunt
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chairez
authors.forename: Raul M
authors.initials: RM
authors.lastname: Alfaro
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D016903:Drug Monitoring; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D041743:Herb-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D005894:Panax / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065692:Cytochrome P-450 CYP3A Inhibitors; D004365:Drugs, Chinese Herbal; D016593:Terfenadine; C093230:fexofenadine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam