Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers.
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.
Weber
A A
AA
Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Braun
M
M
Hohlfeld
T
T
Schwippert
B
B
Tschöpe
D
D
Schrör
K
K
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
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine