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Possible Differential Induction of Phase 2 Enzyme and Antioxidant Pathways by American Ginseng, Panax quinquefolius

From the Division of Clinical Pharmacology, Department of Medicine (Dr Lee, Dr Parsons, Dr Flexner, Dr Lietman) and the Department of Pharmacology and Molecular Sciences (Flexner, Lietman), Johns Hopkins University, Baltimore, Maryland; and Lilly-NUS Centre for Clinical Pharmacology, National University of Singapore, Singapore (Dr Wise, Mr Chan).

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 µg/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 AUC_0-8 (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.

Key Words: Ginseng • zidovudine • oxidative stress • uridine diphosphate glucuronosyltransferase

Address for correspondence: Paul S. Lietman, MD, PhD, 1830 E. Monument Street, Suite 7100, Baltimore, MD 21205; e-mail: plietman{at}jhmi.edu.