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KMID : 0352720160400040375
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Journal of Ginseng Research
2016 Volume.40 No. 4 p.375 ~ p.381
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Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers
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Kim Dal-Sik
Kim Yun-jeong
Jeon Ji-Young
Kim Min-Gul
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Abstract
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Background: 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.
Methods: 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.
Results: 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 (0.805e0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800e0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938e1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864e2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658e1.032) 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 (0.845e1.098). 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.
Conclusion: RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions. Clinical trial registration number (ClinicalTrials.gov): NCT02056743
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KEYWORD
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cytochrome P450, drug interaction, P-glycoprotein, Red Ginseng
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