Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers

• Published in: Journal of ginseng research 2016, 40(4), , pp.375-381
• Main Authors: Kim, Dal-Sik, Kim, Yunjeong, Jeon, Ji-Young, Kim, Min-Gul
• Format: Article
• Language: English
• Subjects: cytochrome P450; drug interaction; P-glycoprotein; Red Ginseng; 기타의약학
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2015.11.005

We evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers. This article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data using analysis of variance after RG administration versus before RG administration. Fourteen healthy male participants were evaluated, none of whom were genetically defined as poor CYP2C9, 2C19, and CYP2D6 metabolizers based on genotyping. Before and after RG administration, the geometric least-square mean metabolic ratio (90% CI) was 0.870 (0.805–0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800–0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938–1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864–2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658–1.032) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time (AUClast) for fexofenadine (P-gp) was 0.963 (0.845–1.098). Administration of concentrated RG for 2 wk weakly inhibited CYP2C9 and CYP3A4 and weakly induced CYP2D6. However, no clinically significant drug interactions were observed between RG and CYP and P-gp probe substrates. RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions. Clinical trial registration number (ClinicalTrials.gov): NCT02056743.