{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:02:13Z","timestamp":1789488133285,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>Although patients with acute coronary syndrome supported by veno\u2010arterial extracorporeal membrane oxygenation (VA\u2010ECMO) have a high risk of thrombosis and bleeding, antiplatelet pharmacology in this setting is not well defined. This prospective observational study investigated the population pharmacokinetics of ticagrelor and its active metabolite AR\u2010C124910XX and explored model\u2010informed dosing strategies among this population. Paired pharmacokinetic sampling was performed at predefined time points during ON\u2010 and OFF\u2010ECMO periods. Plasma concentrations were measured using a validated liquid chromatography\u2013tandem mass spectrometry assay and analyzed with NONMEM to develop a joint parent\u2013metabolite model and evaluate the effects of VA\u2010ECMO status and flow rate on ticagrelor disposition. Monte Carlo simulations of various ECMO flow\u2010rate scenarios examined alternative loading and maintenance regimens using prespecified trough concentrations of 180\u2013360\u2009ng\/mL, as derived from previous exposure\u2013response and exposure\u2010bleeding analyses in non\u2010ECMO populations. A total of 225 ticagrelor and 225 metabolite concentrations (127 ON\u2010ECMO and 98 OFF\u2010ECMO) from 20 patients were analyzed. VA\u2010ECMO support was associated with reduced ticagrelor clearance and increased volume of distribution, while higher flow rates were associated with decreased volumes of distribution. In simulations, an initial loading dose of 120\u2013135\u2009mg followed by a 60\u2009mg maintenance dose once daily most consistently maintained predicted trough concentrations within the target range during VA\u2010ECMO, whereas 90\u2009mg once daily frequently exceeded the upper bound. These findings indicate that VA\u2010ECMO substantially altered ticagrelor pharmacokinetics and provided quantitative, model\u2010informed support for reduced once daily dosing strategies; however, further pharmacokinetic\u2010pharmacodynamic and outcome studies are needed to confirm these findings.<\/jats:p>","DOI":"10.1002\/cpt.70282","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:24:53Z","timestamp":1776169493000},"page":"193-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics of Ticagrelor during Veno\u2010Arterial\n                    <scp>ECMO<\/scp>\n                    in Acute Coronary Syndrome: Model\u2010Informed Dosing Simulations"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-8252","authenticated-orcid":false,"given":"Soyoung","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Mokpo National University  Muan Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Science Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-1421","authenticated-orcid":false,"given":"Kyoung Lok","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicine and Regulatory Science Yonsei University  Incheon Republic of Korea"},{"name":"Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-2954","authenticated-orcid":false,"given":"Seungwon","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Kyung Hee University  Seoul Republic of Korea"},{"name":"Institute of Regulatory Innovation through Science Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7841-8349","authenticated-orcid":false,"given":"Jongsung","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jeonbuk National University  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasohm","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicine and Regulatory Science Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-4076","authenticated-orcid":false,"given":"Byung Hak","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Clinical Trials Center, Severance Hospital, Yonsei University Health System  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Uk","family":"Chae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences The Catholic University of Korea  Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-7187","authenticated-orcid":false,"given":"Soo Kyung","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences The Catholic University of Korea  Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-5130","authenticated-orcid":false,"given":"Jin","family":"Wi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine Gachon University Gil Medical Center  Incheon Republic of Korea"},{"name":"Division of Cardiology, Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-5907","authenticated-orcid":false,"given":"Min Jung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicine and Regulatory Science Yonsei University  Incheon Republic of Korea"},{"name":"Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences Yonsei University  Incheon Republic of Korea"},{"name":"Graduate Program of Industrial Pharmaceutical Science Yonsei University  Incheon Republic of Korea"},{"name":"Department of Integrative Biotechnology &amp; 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