{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:15:30Z","timestamp":1747746930403},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T00:00:00Z","timestamp":1118707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:p><jats:bold>Background:\u2002<\/jats:bold> Paracetamol (acetaminophen) is an effective analgesic and a weak inhibitor of cyclo\u2010oxygenase (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.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Blood was collected from healthy donors and platelet function was assessed by photometric aggregometry, a platelet function analyser (PFA\u2010100\u2122, Dade Behring, Deerfield, IL) and by measuring the release of thromboxane B<jats:sub>2<\/jats:sub> (TxB<jats:sub>2<\/jats:sub>), the stable metabolite of thromboxane A<jats:sub>2<\/jats:sub>, after addition of paracetamol (10\u201380\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup>). A concentration\u2010inhibition relationship was established and the inhibition coefficient (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>) demonstrating 50% binding to COX was determined using a Schild\u2010plot. Interaction of paracetamol (5\u201320\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup>) and diclofenac (0.1\u20130.8\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup>) was determined and an isobolographic analysis was performed.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Paracetamol added to platelet\u2010rich plasma (PRP) caused a concentration\u2010dependent inhibition of platelet function. Photometric aggregometry and TxB<jats:sub>2<\/jats:sub> release was significantly inhibited by paracetamol from 10\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup> onwards. The PFA\u2010100\u2122 closure time was significantly prolonged by paracetamol at a high concentration only. <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> was 15.2\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup> with a 95% confidence interval of 11.8\u201318.6\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup>. Inhibition of aggregation by diclofenac was augmented by paracetamol. Isobolographic analysis showed synergism.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> The 95% confidence interval of K<jats:sub>i<\/jats:sub> equals the antipyretic plasma concentration of paracetamol, i.e. 10\u201320\u2003\u00b5g\u2003ml<jats:sup>\u22121<\/jats:sup>. High doses of paracetamol and a combination of diclofenac and paracetamol cause platelet inhibition and thus may increase risk of surgical bleeding.<\/jats:p>","DOI":"10.1111\/j.1399-6576.2005.00707.x","type":"journal-article","created":{"date-parts":[[2005,6,14]],"date-time":"2005-06-14T10:52:08Z","timestamp":1118746328000},"page":"840-846","source":"Crossref","is-referenced-by-count":21,"title":["Characterization of inhibition of platelet function by paracetamol and its interaction with diclofenac <i>in vitro<\/i>"],"prefix":"10.1111","volume":"49","author":[{"given":"E.","family":"Munsterhjelm","sequence":"first","affiliation":[]},{"given":"T. T.","family":"Niemi","sequence":"additional","affiliation":[]},{"given":"O.","family":"Ylikorkala","sequence":"additional","affiliation":[]},{"given":"M.","family":"Silvanto","sequence":"additional","affiliation":[]},{"given":"P. H.","family":"Rosenberg","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,6,14]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/88.2.215"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/240410a0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162468699"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2232"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.2000.440113.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(85)90005-2"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7563"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(75)90186-0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199733030-00003"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeg195"},{"key":"e_1_2_6_12_2","first-page":"67","article-title":"Quantitative investigations into the aggregation of blood platelets","volume":"162","author":"Born GVR","year":"1962","journal-title":"J Physiol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(80)90114-8"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)89091-4"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00041-6"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01880.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29108"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000138941"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003643-200219251-00003"},{"key":"e_1_2_6_21_2","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1055\/s-0038-1651037","article-title":"Effect of the concentration of Ca2+ in the suspending medium on the responses of human and rabbit platelets to aggregating agents","volume":"62","author":"Packham MA","year":"1989","journal-title":"Thromb Haemostas"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(99)00152-8"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1055\/s-0037-1613805","article-title":"Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA\u2010100","volume":"83","author":"Homoncik M","year":"2000","journal-title":"Thromb Haemostas"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(02)00405-X"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02956-4"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1997.tb04657.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200121070-00002"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.4.870"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200161080-00010"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-200002000-00035"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.2003.00046.x"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199908000-00019"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-199714060-00005"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199708000-00019"}],"container-title":["Acta Anaesthesiologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-6576.2005.00707.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-6576.2005.00707.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T20:54:53Z","timestamp":1696884893000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-6576.2005.00707.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,14]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,7]]}},"alternative-id":["10.1111\/j.1399-6576.2005.00707.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-6576.2005.00707.x","archive":["Portico"],"relation":{},"ISSN":["0001-5172","1399-6576"],"issn-type":[{"value":"0001-5172","type":"print"},{"value":"1399-6576","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,14]]}}}