Siberian Ginseng (Eleutherococcus Senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers

Donovan JL, DeVane CL, Chavin KD, et al.

Objective To assess the influence of a standardized Siberian ginseng [(SG); Eleutherococcus senticosus] extract, one of the 10 most popular herbal supplements, on the activity of cytochrome P450 CYP2D6 and 3A4. Method Using dextromethorphan (DM) as a probe drug for CYP2D6 and alprazolam (ALPZ) for CYP3A4 activity, 12 normal volunteers (7 men) between the ages of 23-44 years who were phenotyped as normal metabolizers of CYP2D6 participated in the study. Participants received 30 mg DM and 2 mg ALPZ. An 8-h urine collection commenced immediately after drug administration. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60-h time points to serve as the baseline measurement of CYP2D6 and CYP3A4 activity. After a minimum 7-day washout period, subjects received a 14-day supply of SG extract (485-mg capsules) to be taken twice daily at specified times. After 14 days, participants returned to the research center and were given the same dosage and sample collection as in the baseline phase. Active ingredients in SG were analyzed to confirm that levels were in agreement with labeled claims. Validated high-performance liquid chromatography methods were used to quantify all compounds and relevant metabolites. Using the paired t test, mean pharmacokinetic parameters and dextromethorphan metabolic ratios (DMRs) were analyzed at baseline and following SG administration. Because sex-specific induction of CYP3A4 has been reported, data were also sorted by sex and analyzed. Results The only adverse event reported by one participant was nausea. CYP2D6 activity was assessed by the ratio of DM to its metabolite. All subjects metabolized DM extensively at baseline and after SG administration. There were no significant differences in the ratios between the baseline and SG phases (P > 0.05). Analysis of ALPZ pharmacokinetics was used to assess CYP3A4 activity. None of the values were significantly different between treatment phases (P > 0.05). Gender differences were not statistically significant. Conclusions Given recent evidence of drug interactions with commonly used herbs, such as St. John's Wort, it becomes increasingly important to assess the potential for botanical-drug interactions with commonly used herbal preparations. However, standardized SG extracts, in the normally recommended doses, do not affect the activity of CYP2D6 or CYP3A4. There appears to be little likelihood of significant botanical-drug interactions between SG and drugs predominantly metabolized by CYP2D6 or CYP3A4 isoforms. Drug Metab Dispos 2003 May;31(5):519-22. Return to Top