Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)
Language English Country Germany Media print-electronic
Document type Journal Article
- MeSH
- Purinergic P2 Receptor Antagonists administration & dosage blood pharmacokinetics MeSH
- Administration, Oral MeSH
- Biological Availability MeSH
- Intubation, Gastrointestinal MeSH
- Platelet Aggregation Inhibitors administration & dosage blood pharmacokinetics MeSH
- Cardiopulmonary Resuscitation * MeSH
- Clopidogrel MeSH
- Percutaneous Coronary Intervention * instrumentation MeSH
- Critical Illness MeSH
- Middle Aged MeSH
- Humans MeSH
- Receptors, Purinergic P2 drug effects metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Stents MeSH
- Tablets MeSH
- Hypothermia, Induced MeSH
- Ticlopidine administration & dosage analogs & derivatives blood pharmacokinetics MeSH
- Blood Platelets drug effects metabolism MeSH
- Thrombelastography MeSH
- Respiration, Artificial MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Purinergic P2 Receptor Antagonists MeSH
- Platelet Aggregation Inhibitors MeSH
- Clopidogrel MeSH
- Receptors, Purinergic P2 MeSH
- Tablets MeSH
- Ticlopidine MeSH
PURPOSE: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. METHODS: In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. RESULTS: The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). CONCLUSION: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.
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