Characterization of inhibition of platelet function by paracetamol and its interaction with diclofenac in vitro
Autor: | E. Munsterhjelm, Per H. Rosenberg, O. Ylikorkala, Tomi T. Niemi, M. Silvanto |
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Rok vydání: | 2005 |
Předmět: |
Adult
Male Diclofenac Platelet Aggregation Platelet Function Tests Thromboxane Analgesic In Vitro Techniques Pharmacology 03 medical and health sciences 0302 clinical medicine medicine Humans Cyclooxygenase Inhibitors Drug Interactions Platelet Antipyretic Acetaminophen 030304 developmental biology 0303 health sciences Arachidonic Acid Dose-Response Relationship Drug biology business.industry Anti-Inflammatory Agents Non-Steroidal digestive oral and skin physiology General Medicine Analgesics Non-Narcotic Middle Aged Platelet Activation 3. Good health Thromboxane B2 Dose–response relationship Anesthesiology and Pain Medicine Prostaglandin-Endoperoxide Synthases Enzyme inhibitor biology.protein Female business Platelet Aggregation Inhibitors 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Acta Anaesthesiologica Scandinavica. 49:840-846 |
ISSN: | 1399-6576 0001-5172 |
DOI: | 10.1111/j.1399-6576.2005.00707.x |
Popis: | Background Paracetamol (acetaminophen) is an effective analgesic and a weak inhibitor of cyclo-oxygenase (COX). Clinically paracetamol is often used together with traditional NSAIDs, which are strong inhibitors of COX. We studied binding of paracetamol to COX and its action on platelet function together with diclofenac. Methods Blood was collected from healthy donors and platelet function was assessed by photometric aggregometry, a platelet function analyser (PFA-100, Dade Behring, Deerfield, IL) and by measuring the release of thromboxane B(2) (TxB(2)), the stable metabolite of thromboxane A(2), after addition of paracetamol (10-80 microg ml(-1)). A concentration-inhibition relationship was established and the inhibition coefficient (K(i)) demonstrating 50% binding to COX was determined using a Schild-plot. Interaction of paracetamol (5-20 microg ml(-1)) and diclofenac (0.1-0.8 microg ml(-1)) was determined and an isobolographic analysis was performed. Results Paracetamol added to platelet-rich plasma (PRP) caused a concentration-dependent inhibition of platelet function. Photometric aggregometry and TxB(2) release was significantly inhibited by paracetamol from 10 microg ml(-1) onwards. The PFA-100 closure time was significantly prolonged by paracetamol at a high concentration only. K(i) was 15.2 microg ml(-1) with a 95% confidence interval of 11.8-18.6 microg ml(-1). Inhibition of aggregation by diclofenac was augmented by paracetamol. Isobolographic analysis showed synergism. Conclusions The 95% confidence interval of K(i) equals the antipyretic plasma concentration of paracetamol, i.e. 10-20 microg ml(-1). High doses of paracetamol and a combination of diclofenac and paracetamol cause platelet inhibition and thus may increase risk of surgical bleeding. |
Databáze: | OpenAIRE |
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