Influence of Panax ginseng on Cytochrome P450 (CYP)3A and P‐glycoprotein (P‐gp) Activity in Healthy Participants

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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 (AUC0‐∞), half‐life (t1/2), and maximum concentration (Cmax) 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.