{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:01:01Z","timestamp":1785366061315,"version":"3.55.0"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006345","name":"Nicolaus Copernicus University in Toru\u0144","doi-asserted-by":"crossref","award":["IND.WL.1.202"],"award-info":[{"award-number":["IND.WL.1.202"]}],"id":[{"id":"10.13039\/501100006345","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Morphine is known to negatively influence the pharmacokinetics (PK) and the antiplatelet effect of oral P2Y12 receptor inhibitors administered due to an acute coronary syndrome. Worldwide studies of the potential approaches to overcome the undesired morphine effect have been only partially successful. The aim of the METHANE-SIRIO 4 study was to evaluate the PK and pharmacodynamics of ticagrelor and its active metabolite in unstable angina (UA) patients treated with morphine or methoxyflurane.<\/jats:p>\n                  <jats:p>Consecutive patients diagnosed with UA, randomized into the study arms, underwent the assessment of platelet reactivity using the Multiplate analyzer at nine predefined study time points. Serum concentrations of ticagrelor and its active metabolite, AR-C124910XX, were measured for each study participant. Median platelet reactivity was significantly lower in patients who received ticagrelor and methoxyflurane versus ticagrelor alone at 30\u2009minutes postticagrelor loading dose. A trend toward lower reactivity was observed at 45 and 240\u2009minutes. Significant differences in median serum concentrations of ticagrelor and its active metabolite were most pronounced between patients treated with ticagrelor and methoxyflurane versus ticagrelor and morphine.<\/jats:p>\n                  <jats:p>Co-administration of methoxyflurane in acute coronary syndrome patients allows for the avoidance of negative effects of morphine and has the additional effect of inhibiting platelet reactivity. Further randomized studies would be recommended to support these findings.<\/jats:p>","DOI":"10.1055\/a-2698-3958","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T23:38:33Z","timestamp":1758238713000},"page":"822-831","source":"Crossref","is-referenced-by-count":0,"title":["Methoxyflurane Instead of Morphine in Acute Coronary Syndrome Patients: Results of the Randomized Controlled METHANE-SIRIO 4 Study"],"prefix":"10.1055","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-9730","authenticated-orcid":false,"given":"Piotr","family":"Niezgoda","sequence":"first","affiliation":[{"name":"Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Podhajski","sequence":"first","affiliation":[{"name":"Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Kasprzak","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Bara\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Rakotoarison","sequence":"additional","affiliation":[{"name":"Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017cena","family":"Karolko","sequence":"additional","affiliation":[{"name":"Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Pietrzykowski","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Michalski","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Kosobucka","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sikora","sequence":"additional","affiliation":[{"name":"The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"},{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University, Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Cha\u0142upka","sequence":"additional","affiliation":[{"name":"The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"},{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University, Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Marsza\u0142\u0142","sequence":"additional","affiliation":[{"name":"The Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6284-0820","authenticated-orcid":false,"given":"Wiktor","family":"Kuliczkowski","sequence":"additional","affiliation":[{"name":"Institute for Heart Diseases, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldona","family":"Kubica","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Kubica","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1055\/a-1739-9351","article-title":"Platelets in myocardial ischemia\/reperfusion injury","volume":"43","author":"N Schanze","year":"2023","journal-title":"Hamostaseologie"},{"issue":"38","key":"ref2","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","article-title":"2023 ESC guidelines for the management of acute coronary syndromes","volume":"44","author":"R A Byrne","year":"2023","journal-title":"Eur Heart J"},{"issue":"03","key":"ref3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/eurheartj\/ehv547","article-title":"Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial","volume":"37","author":"J Kubica","year":"2016","journal-title":"Eur Heart J"},{"issue":"07","key":"ref4","first-page":"630","article-title":"Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial","volume":"63","author":"E L Hobl","year":"2014","journal-title":"J Am Coll Cardiol"},{"issue":"15","key":"ref5","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.jacc.2013.01.024","article-title":"Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (rapid activity of platelet inhibitor drugs) primary PCI study","volume":"61","author":"G Parodi","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.3390\/jcm12062374","article-title":"Pretreatment with P2Y12 receptor inhibitors in acute coronary syndromes-is the current standpoint of ESC experts sufficiently supported?","volume":"12","author":"P Niezgoda","year":"2023","journal-title":"J Clin Med"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1160\/TH17-03-0154","article-title":"Prasugrel in critically ill patients","volume":"117","author":"C Schoergenhofer","year":"2017","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13049-020-00731-y","article-title":"Nitrous oxide\/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study","volume":"28","author":"S Charpentier","year":"2020","journal-title":"Scand J Trauma Resusc Emerg Med"},{"issue":"08","key":"ref9","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1055\/s-0038-1666862","article-title":"Fentanyl delays the platelet inhibition effects of oral ticagrelor: full report of the PACIFY randomized clinical trial","volume":"118","author":"K 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