title: The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects.
abstract: OBJECTIVE
  The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol.
  
  
  METHODS
  A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment.
  
  
  RESULTS
  The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBE vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments.
  
  
  CONCLUSIONS
  Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Korea; Department of Clinical Pharmacology, Inje University Busan Paik Hosptial, Busan, Korea.
authors.forename: Ho-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Yeo
authors.forename: Minkyung
authors.initials: M
authors.lastname: Oh
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Ghim
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D000328:Adult; D019540:Area Under Curve; D000077407:Cilostazol; D018592:Cross-Over Studies; D004311:Double-Blind Method; D020441:Ginkgo biloba; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D013777:Tetrazoles / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; D013777:Tetrazoles; D000077407:Cilostazol
keywords: Ginkgo biloba extracts; cilostazol; herb-drug interaction; pharmacodynamics; pharmacokinetics