European Journal of Clinical Pharmacology

, Volume 69, Issue 11, pp 1883–1890 | Cite as

The effect of grape seed extract on the pharmacokinetics of dextromethorphan in healthy volunteers

  • Andrew K. L. GoeyEmail author
  • Irma Meijerman
  • Jos H. Beijnen
  • Jan H. M. Schellens
Clinical Trial



Grape seed extract (GSE) has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. To determine the clinical effect of GSE on CYP2D6, the pharmacokinetic interaction between GSE and the sensitive CYP2D6 probe dextromethorphan in healthy adult volunteers was examined.


In this open label, randomized, cross-over study, 30 subjects were assigned to cohort A or B. Both cohorts ingested 30 mg dextromethorphan hydrobromide on day 1 and day 10. Cohort A received 100 mg GSE capsules three times daily on days 8, 9 and 10, while cohort B started with GSE on day −1 until day 1. After urine collection (0–8 h) on day 1 and day 10, the urinary dextromethorphan to dextrorphan metabolic ratio was determined.


Among 28 evaluable subjects, an increase of the urinary metabolic ratio was observed in 16 subjects (57 %). The mean metabolic ratio (± standard deviation) before and after GSE supplementation was 0.41 (± 0.56) and 0.48 (± 0.59), respectively. This result was neither statistically (P = 0.342) nor clinically [geometric mean ratio 1.10, 90 % CI (0.93–1.30)] significant. Further, the majority (73 %) of the included subjects did not experience any adverse events after intake of dextromethorphan or GSE.


Supplementation of GSE did not significantly affect the urinary dextromethorphan to dextrorphan metabolic ratio in healthy volunteers. The results of this clinical study indicate that GSE appears to be safe to combine with drugs extensively metabolized by CYP2D6, such as dextromethorphan and tamoxifen.


Pharmacokinetics Dextromethorphan Grape seed extract CYP2D6 Herb-drug interactions Clinical trial 



This study was supported by a project grant (UU 2007–3795) of the Dutch Cancer Society (KWF Kankerbestrijding). Furthermore, we would like to thank Miriam Warnier, MD and Talitha Verhoef, MD (Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University) for executing the venipunctures.

Conflicts of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Andrew K. L. Goey
    • 1
  • Irma Meijerman
    • 2
  • Jos H. Beijnen
    • 1
    • 3
  • Jan H. M. Schellens
    • 1
    • 4
  1. 1.Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical PharmacologyUtrecht UniversityUtrechtThe Netherlands
  2. 2.Department of Pharmaceutical Sciences, Division of PharmacologyUtrecht UniversityUtrechtThe Netherlands
  3. 3.Department of Pharmacy & PharmacologySlotervaart Hospital/The Netherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.Department of Clinical PharmacologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands

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