title: Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers.
abstract: OBJECTIVE
  To study the recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers.
  
  
  METHODS
  Ten healthy volunteers were treated with clopidogrel (75 mg day(-1)) for 7 days. CD62P expression and PAC-1 binding were measured by flow cytometry.
  
  
  RESULTS
  Adenosine diphosphate (ADP, 30 microM)-induced platelet responses were almost completely inhibited by clopidogrel. After discontinuation of the drug, platelet function gradually increased and complete recovery was seen 7 days after the last clopidogrel dose. The mean difference (95% CI) for ADP-induced PAC-1 binding (fluorescence intensity) between baseline and 7 days after the last dose was 0.01 (0.61, -0.59). Single cell analysis provides direct evidence for an irreversible mode of action of clopidogrel.
  
  
  CONCLUSIONS
  This is the first report to directly demonstrate irreversibility of clopidogrel action in humans.
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: A A
authors.initials: AA
authors.lastname: Weber
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.forename: T
authors.initials: T
authors.lastname: Hohlfeld
authors.forename: B
authors.initials: B
authors.lastname: Schwippert
authors.forename: D
authors.initials: D
authors.lastname: Tschöpe
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000077144:Clopidogrel; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine