Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers

• Published in: British journal of clinical pharmacology Vol. 52; no. 3; pp. 333 - 336
• Main Authors: Weber, Artur‐Aron, Braun, Marina, Hohlfeld, Thomas, Schwippert, Barbara, Tschöpe, Diethelm, Schrör, Karsten
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2001; Blackwell Science; Blackwell Science Inc
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Binding, Competitive - drug effects; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Platelets - physiology; Blood. Blood coagulation. Reticuloendothelial system; Clopidogrel; Flow Cytometry; Humans; irreversibility; Male; Medical sciences; P-Selectin - drug effects; P-Selectin - metabolism; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; platelets; Short Reports; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Time Factors; Human; Platelet; Healthy subject; Treatment withdrawal; Clopidogrel; ADP; Biological activity; Antiplatelet agent; Duration of action
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.0306-5251.2001.01453.x

Aims  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 µM)‐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.