title: Possible differential induction of phase 2 enzyme and antioxidant pathways by american ginseng, Panax quinquefolius.
abstract: Human immunodeficiency virus (HIV)-infected patients often take herbal medicines, which may interact with antiretrovirals. American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsenoside-enriched American ginseng extract 200 mg twice daily. This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 microg/mL. Total ginsenoside content was 8.5 +/- 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post-zidovudine dose. American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide (ratio post- to pre-American ginseng = 1.17; 90% confidence interval: 0.95-1.45; P = .21), total clearance (ratio = 0.97; 0.82-1.14; P = .70), or plasma zidovudine AUC0-8 (ratio = 1.03; 0.87-1.21; P = .77). Oxidative stress biomarkers are reduced post-American ginseng (F2-isoprostane ratio = 0.79; 0.72-0.86; P < .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lee
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wise
authors.forename: Clark
authors.initials: C
authors.lastname: Chan
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Parsons
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.forename: Paul S
authors.initials: PS
authors.lastname: Lietman
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D019380:Anti-HIV Agents / Q000493:pharmacokinetics; D000975:Antioxidants / Q000378:metabolism; D019540:Area Under Curve; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000097:blood / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D019380:Anti-HIV Agents; D000975:Antioxidants; D054316:Biomarkers, Pharmacological; D028441:F2-Isoprostanes; D036145:Ginsenosides; D017320:HIV Protease Inhibitors; D010936:Plant Extracts; D015215:Zidovudine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C055886:3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine; D016660:NAD(P)H Dehydrogenase (Quinone); D003849:Deoxyguanosine