Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

• Published in: European journal of clinical pharmacology 2013-03, Vol.69 (3), p.309-317
• Main Authors: Součková, L., Opatřilová, R., Suk, P., Čundrle, I., Pavlík, M., Zvoníček, V., Hlinomaz, O., Šrámek, V.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Bioavailability; Biological and medical sciences; Biological Availability; Biomedical and Life Sciences; Biomedicine; Blood Platelets - drug effects; Blood Platelets - metabolism; Cardiopulmonary Resuscitation; Chromatography, High Pressure Liquid; CPR; Critical Illness; Drug therapy; Female; Humans; Hypothermia, Induced; Intubation, Gastrointestinal; Male; Medical sciences; Middle Aged; Patients; Percutaneous Coronary Intervention - instrumentation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - blood; Platelet Aggregation Inhibitors - pharmacokinetics; Purinergic P2 Receptor Antagonists - administration & dosage; Purinergic P2 Receptor Antagonists - blood; Purinergic P2 Receptor Antagonists - pharmacokinetics; Receptors, Purinergic P2 - drug effects; Receptors, Purinergic P2 - metabolism; Respiration, Artificial; Review Article; Stents; Tablets; Thrombelastography; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - blood; Ticlopidine - pharmacokinetics
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-012-1360-0

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