title: Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers.
abstract: OBJECTIVE
  We assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761® with respect to the activities of major cytochrome P450 (CYP) enzymes.
  
  
  METHODS
  A single-center, open-label, randomized, three-fold crossover, cocktail phenotyping design was applied. In random order, the following treatments were administered to 18 healthy men and women for 8 days each: placebo twice daily, EGb 761® 120 mg twice daily, and EGb 761® 240 mg in the morning and placebo in the evening. In the morning of day 8, administration was performed together with the orally administered phenotyping cocktail (enzyme, metric): 150 mg caffeine (CYP1A2, paraxanthine/caffeine plasma ratio 6-h postdose), 125 mg tolbutamide (CYP2C9, plasma concentration 24-h postdose), 20 mg omeprazole (CYP2C19, omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose), 30 mg dextromethorphan (CYP2D6, dextromethorphan/dextrorphan plasma ratio 3-h postdose), and 2 mg of midazolam (CYP3A, plasma concentration 6-h postdose). Formally, absence of a relevant interaction was assumed if the 90% confidence intervals (CIs) for EGb 761®/placebo ratios of the metrics were within the 0.70-1.43 range.
  
  
  RESULTS
  EGb 761®/placebo ratios for phenotyping metrics were close to unity for all CYPs. Furthermore, respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761® 120 mg twice daily (90% CI 0.681-1.122) and for CYP2D6 for EGb 761® 240 mg once daily (90% CI 0.667-1.281). These findings were attributed to the intraindividual variability of the metrics used. All treatments were well tolerated.
  
  
  CONCLUSIONS
  EGb 761® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug-drug interactions.
authors.affiliation: Department of Pharmacology Clinical Pharmacology Unit, University of Cologne, Gleueler Str. 24, 50931, Cologne, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Zadoyan
authors.forename: D
authors.initials: D
authors.lastname: Rokitta
authors.forename: S
authors.initials: S
authors.lastname: Klement
authors.forename: A
authors.initials: A
authors.lastname: Dienel
authors.forename: R
authors.initials: R
authors.lastname: Hoerr
authors.forename: T
authors.initials: T
authors.lastname: Gramatté
authors.forename: U
authors.initials: U
authors.lastname: Fuhr
mesh_terms: D000328:Adult; D001711:Biotransformation / Q000187:drug effects; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D019587:Dietary Supplements / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000097:blood; D006261:Headache / Q000139:chemically induced; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D010641:Phenotype; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult; D000096983:Ginkgo Extract
chemical_list: D002110:Caffeine; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D046934:Ginkgolides; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract