title: Ticlopidine with Ginkgo Biloba extract: a feasible combination for patients with acute cerebral ischemia.
abstract: BACKGROUND
  Even though clopidogrel is the most used drug for cardiovascular prevention, resistance occurs in significant numbers. Therefore, we evaluated platelet aggregation ability of thienopyridines in relation with various genotypes.
  
  
  METHODS
  The study population was randomly assigned with clopidogrel (n=43), ticlopidine (n=41), or ticlopidine plus Gingko Biloba extract (EGb) (n=43). Dosage was maintained as 75mg clopidogrel daily, 250mg ticlopidine twice daily, and 250mg ticlopidine plus 80mg Gingko Biloba extract twice daily. Using multiple electrodes aggregometry, platelet aggregation was measured by activators of adenosine diphosphate (ADP), arachidonic acid (ASP), and thrombin (TRAP) at baseline (T0), 7days (T1), and 90days (T2). Side-effects were analyzed in the 3 groups. Inhibition of platelet aggregation (IPA) was defined as percent decrease at T0 and T1. Non-responsiveness (<IPA 20%) was analyzed according to cytochrome P450 polymorphisms.
  
  
  RESULTS
  There was no difference of general demographics and platelet aggregation at baseline in all groups. A significant difference of platelet aggregation showed on ADP test in the groups at T1 (28.9±17.2 vs.22.7±11.1 vs. 14.6±10.3%, p<0.001) and T2 (27.5±24.5 vs.18.3±16.6 vs. 14.4±9.8%, p=0.007), whereas ASP (p=0.064) and TRAP tests (p=0.143) had no differences at T1. Serious adverse events had no differences among the groups (p=0.902). CYP2C19 *2 alleles had poor responsiveness of clopidogrel (p=0.038), and not in ticlopidine (p=0.780).
  
  
  CONCLUSIONS
  This finding suggests that ticlopidine plus Gingko Biloba extract has sufficient anti-platelet abilities with an acceptable profile of adverse events and CYP2C19 *2 alleles are associated with clopidogrel responsiveness.
authors.affiliation: Department of Neurology, Ajou University School of Medicine, Suwon, South Korea. dacda@hanmail.net
authors.forename: Ji Man
authors.initials: JM
authors.lastname: Hong
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Lim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: In Soo
authors.initials: IS
authors.lastname: Joo
mesh_terms: D000208:Acute Disease; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010936:Plant Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine