Multiple-Dose Administration of Ginkgo biloba Did Not Affect Cytochrome P-450 2D6 or 3A4 Activity in Normal Volunteers

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Abstract
Standardized extracts from the Ginkgo biloba tree are purported to exert positive neurocognitive effects and may also be useful in the treatment of a variety of vascular and other disorders. This dietary supplement is among the most commonly used herbal preparations in the world. The objective of this study was to assess in normal volunteers (n = 12) the influence of standardized Ginkgo biloba (GB) on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 normal volunteers phenotyped as CYP2D6 extensive metabolizers. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP 3A4 activity) were co-administered orally at baseline, and following treatment with GB (120 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after GB treatment. Likewise, plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetics at baseline and after GB treatment to assess effects on CYP 3A4 activity. Validated HPLC methods were used to quantify all compounds and relevant metabolites. No statistically significant differences were found between baseline and post-GB treatment DMRs indicating a lack of effect on CYP2D6. For alprazolam there was a 17% decrease in the area under the plasma concentration versus time curve (AUC); (P<0.05). However, the half-life of elimination was not significantly different after GB administration indicating a lack of hepatic CYP3A4 induction. We conclude that standardized extracts of GB at recommended doses are unlikely to significantly alter the disposition of co-administered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.