title: Ex vivo--in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A.
abstract: OBJECTIVE
  To assess the interaction between aspirin and clopidogrel in healthy male volunteers and the interaction of the glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors abciximab and SR121566A with blood from those pretreated subjects (ex vivo-in vitro).
  
  
  METHODS
  Aspirin (300 mg/day), clopidogrel (75 mg/day), or the combination of both drugs were administered orally for 8 days. Group 1 (n = 5) started with aspirin and group 2 (n = 5) with clopidogrel. From day 4 to day 8, subjects of both groups received the combined treatment. Blood from these subjects was spiked with abciximab (0.5 and 1.5 microg x mL(-1)) and SR121566A (31 and 62 ng x mL(-1)).
  
  
  RESULTS
  In vivo, average bleeding times were 6.8 minutes at baseline, 20.3 minutes for clopidogrel alone (P < .01), 10.9 minutes for aspirin alone (difference not significant), and 24.0 minutes (P < .01) for the combined treatment. Fibrinogen binding to the platelet GPIIb/IIIa receptor was reduced for aspirin to 69% (difference not significant), to 63% for clopidogrel (difference not significant), and to 63% for the clopidogrel plus aspirin combination (P < .01). CD62 expression as a marker of platelet granular secretion was reduced to 66% by clopidogrel (P < .01) and to 41% by the combination of clopidogrel and aspirin; aspirin alone had no effect. In vitro, with pretreatment with aspirin and clopidogrel, inhibitory effects of the GPIIb/IIIa inhibitors on fibrinogen binding were additive to changes observed with aspirin or clopidogrel alone. No effect on CD62 expression was observed with either GPIIb/IIIa inhibitor. Aspirin and clopidogrel reinforced effects of the GPIIb/IIIa inhibitors on adenosine diphosphate (5 micromol/L)-induced aggregation in an additive manner, a supra-additive effect was observed with collagen (2 microg x mL(-1))-induced aggregation.
  
  
  CONCLUSIONS
  The augmentation of the antiaggregatory effects of GPIIb/IIIa inhibitors by aspirin and clopidogrel and the lack of antisecretory effects of GPIIb/IIIa inhibitors may favor their combination with clopidogrel.
authors.affiliation: Institute of Clinical Pharmacology of the JW Goethe University and the International Institute of Thrombosis and Vascular Diseases, Frankfurt am Main, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: C M
authors.initials: CM
authors.lastname: Kirchmaier
authors.forename: D
authors.initials: D
authors.lastname: Westrup
authors.forename: J
authors.initials: J
authors.lastname: Graff
authors.forename: R
authors.initials: R
authors.lastname: Mahnel
authors.forename: H K
authors.initials: HK
authors.lastname: Breddin
authors.forename: S
authors.initials: S
authors.lastname: Harder
mesh_terms: D000077284:Abciximab; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001596:Benzylamines; D001760:Bleeding Time; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009391:Nephelometry and Turbidimetry; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D013844:Thiazoles; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D001596:Benzylamines; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C106774:SR 121566; D013844:Thiazoles; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D000077284:Abciximab