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

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 subjects (8 males) 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 pre-and post P. ginseng administration. Geometric mean ratios (post-ginseng/pre-ginseng) for midazolam area under the concentration vs. 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, Panax ginseng appeared to induce CYP3A activity in the liver and possibly the gastrointestinal tract. Patients taking Panax ginseng in combination with CYP3A substrates with narrow therapeutic ranges should be monitored closely for adequate therapeutic response to the substrate medication.

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis

“…In the current study, we showed that GSE significantly attenuated DSS-induced colitis, which is associated with repressed NF-kB activity and restored PXR and CYP3A mRNA expression in the inflamed colon. Although it has previously been reported that Panax ginseng influence CYP3A activity (Malati et al, 2012), we confirmed that ginsenosides had no effect on Pxr and Cyp3a11 mRNA expression in the healthy mice, which is consistent with the findings from in vitro LS174T cells and the results from other groups (Gurley et al, 2002;Anderson et al, 2003).…”

Panax ginseng inhibits intestinal absorption of toxic Aconitum carmichaeli alkaloids in Vitro

“…However, Malati's group suggested that (using fexofenadine as a probe substrate) ginseng did not alter P-gp function in healthy volunteers. (31) Two ideas may explain the difference between our data. First fexofenadine as a P-gp probe is not specifi c. The transport system for fexofenadine includes not only P-gp but also other transporters.…”

Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences

“…Comparison of pharmacokinetic parameter values of midazolam was calculated and compared before and following the administration of Panax ginseng. As illustrated in Figure 4, the findings revealed significant reduction for midazolam area under the concentration-time curve from zero to infinity, half-life and maximum concentration [104]. Also, American ginseng (Panax quinquefolius)…”

“…Panax ginseng is a widely used herbal medicine, notably used for its antidepressant effect. A study investigated the influence of Panax ginseng on CYP3A function using the probe midazolam as a substrate probe [104]. Comparison of pharmacokinetic parameter values of midazolam was calculated and compared before and following the administration of Panax ginseng.…”