title: The effect of grape seed extract on the pharmacokinetics of dextromethorphan in healthy volunteers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands, andrewgoey@hotmail.com.
authors.forename: Andrew K L
authors.initials: AK
authors.lastname: Goey
authors.forename: Irma
authors.initials: I
authors.lastname: Meijerman
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000328:Adult; D000996:Antitussive Agents / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D003915:Dextromethorphan / Q000493:pharmacokinetics* / Q000652:urine; D003917:Dextrorphan / Q000652:urine; D004347:Drug Interactions; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000996:Antitussive Agents; D056604:Grape Seed Extract; D003917:Dextrorphan; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6