{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:18:15Z","timestamp":1791235095424,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP\u20107041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo\u2010 and positive\u2010controlled, sequential, ascending\u2010dose (0.3\/0.6\/1.0\/1.5\/2.25\u2009mg\/kg\/h) study of 5\u2010day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50\u2009h. The mean half\u2010life ranged from 1.15 to 1.43\u2009h. Frunexian plasma concentration at a steady state and area under the concentration\u2013time curve exhibited dose\u2010proportional increases. The dose\u2010escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT\/baseline and FXI clotting activity\/baseline) were described by the two\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    models, with the EC\n                    <jats:sub>50<\/jats:sub>\n                    values of 8940 and 1300\u2009ng\/mL, respectively. Frunexian exhibits good safety and PK\/PD properties, suggesting it is a promising candidate for anticoagulant drug.\n                  <\/jats:p>","DOI":"10.1111\/cts.13787","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T05:59:29Z","timestamp":1711951169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose\u2010escalation phase I study"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-0232","authenticated-orcid":false,"given":"Jia\u2010yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zou\u2010rong","family":"Ruan","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-0959","authenticated-orcid":false,"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7168-0364","authenticated-orcid":false,"given":"Dan\u2010dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-9484","authenticated-orcid":false,"given":"Jia\u2010ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Hu","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang University, School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6899-0328","authenticated-orcid":false,"given":"Yong\u2010rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan Haisco Pharmaceutical Co., Ltd.  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