{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T06:41:29Z","timestamp":1696401689331},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,29]],"date-time":"2014-03-29T00:00:00Z","timestamp":1396051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antiplatelet agents are a class of pharmaceuticals that decrease platelet aggregation and thus inhibit thrombus formation. We examined the relationships between plasma concentrations of antiplatelet agents (triflusal, clopidogrel and cilostazol) and the platelet aggregation inhibitory effect after dosing. We used triflusal, cilostazol and clopidogrel for the development of a semi\u2010mechanistic <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> model. The drugs chosen are used widely and reflect various mechanisms of antiplatelet agents. Time courses of plasma concentrations of the antiplatelet agents and their platelet aggregation effects were analysed using <jats:styled-content style=\"fixed-case\">ADPAT<\/jats:styled-content> V. Pharmacokinetic profiles were fitted to an extended parent\u2013metabolite pharmacokinetic model, based on a two\u2010compartment model, and the pharmacodynamic effects of the agents were fitted to a platelet aggregation effect model that consisted of the following parameters: <jats:italic>K<\/jats:italic><jats:sub>s<\/jats:sub>, the active\u2010form platelet synthesis rate constant; <jats:italic>K<\/jats:italic>, the apparent reaction rate constant of the agent and active\u2010form platelets; <jats:italic>K<\/jats:italic><jats:sub>el\u2010PRP<\/jats:sub>, the apparent rate constant of platelets; and \u03b5, an intrinsic activity parameter. This semi\u2010mechanistic <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> model described well the relationship between plasma concentrations of antiplatelet agents and platelet aggregation effects. In addition, the estimated parameters were suitable for the explanation of the agents and also have a good correlation with platelet characteristics, such as platelet half\u2010life and platelet aggregation baseline effects. Specifically, we discovered the strong correlations between estimated <jats:italic>K<\/jats:italic> parameter and <jats:italic>in vitro<\/jats:italic> drug activity. We conclude that this semi\u2010mechanistic PK\/PD model explained drug PK\/PD characteristics well and will be useful for accurate predictions of antiplatelet effect in the clinical situations.<\/jats:p>","DOI":"10.1111\/bcpt.12222","type":"journal-article","created":{"date-parts":[[2014,2,24]],"date-time":"2014-02-24T18:17:42Z","timestamp":1393265862000},"page":"352-359","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Semi\u2010Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents"],"prefix":"10.1111","volume":"115","author":[{"given":"Hwi\u2010yeol","family":"Yun","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungnam National University Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonku","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yeungnam University Gyeongsan Korea"},{"name":"College of Pharmacy Chung\u2010Ang University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung\u2010yo","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunkyung","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yeungnam University Gyeongsan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Ran","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Clinical Trial Center Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yeul Ma","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM)\u2010Based Herbal Drug Development Group Korea Institute of Oriental Medicine Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang\u2010il","family":"Kwon","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.2.514.514"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-199914010-00005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199855060-00011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010746"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.122474"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03189971"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH04-02-0105"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.630661"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2006.08.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020995013200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9282-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100139"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200401000-00012"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847020-00006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2008.02.013"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1316374"}],"container-title":["Basic &amp; 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