{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:31:41Z","timestamp":1790706701385,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ropeginterferon alfa\u20102b (ropeg) represents a new\u2010generation interferon\u2010based therapy approved for polycythaemia vera (PV) treatment. This study aimed to elucidate its population pharmacokinetics\u2010pharmacodynamics (PopPK\u2010PD) and exposure\u2010response (E\u2010R) relationships. A PopPK model was developed using pooled data from four clinical studies, including two Phase I studies in healthy volunteers (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200948) and two Phase II studies in Chinese or Japanese patients with PV (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200978). Sequential modeling was used to analyze pharmacokinetics\u2010pharmacodynamics (PK\u2010PD) regarding hematological parameters, including hematocrit, platelet, and white blood cell counts. Hematological changes were simulated using fast\u2010 and slow\u2010dose titration regimens. Individual exposure values were used to analyze the E\u2010R relationships regarding complete hematologic response (CHR), driver mutation,\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F allele burden, and safety. In this study, we developed a target\u2010mediated drug disposition model. Sigmoid indirect effects elucidated the PK\u2010PD in terms of hematological changes. Simulations showed that the fast\u2010titration regimen significantly accelerated hematocrit reduction. Logistic regression models showed that the probability of achieving CHR increased with exposure at Week 24 but not at Week 52. In contrast,\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F allele reductions correlated with exposure at both Weeks 24 and 52. Exposure\u2010safety analysis revealed a manageable risk of adverse events associated with transaminase increases. This study established a robust framework for ropeg PK\u2010PD, providing insights into its E\u2010R relationships and disease\u2010modifying action.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    A17\u2010102, A19\u2010201, and A20\u2010202 are registered at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    . The registration numbers are as follows: A17\u2010102, NCT03546465; A19\u2010201, NCT04182100; and A20\u2010202, NCT05485948. A17\u2010101 is registered at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chinadrugtrials.org.cn\">www.chinadrugtrials.org.cn<\/jats:ext-link>\n                    . The registration number is CTR20190451\n                  <\/jats:p>","DOI":"10.1002\/prp2.70109","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:29:37Z","timestamp":1746174577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetics\u2010Pharmacodynamics and Exposure\u2010Response of Ropeginterferon Alfa\u20102b in Chinese and Japanese Patients With Polycythemia Vera"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7610-084X","authenticated-orcid":false,"given":"Albert","family":"Qin","sequence":"first","affiliation":[{"name":"Medical Research &amp; Clinical Operations, PharmaEssentia Corporation  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Division of Haematology, Diabetes and Endocrinology, Department of Internal Medicine, Faculty of Medicine University of Miyazaki  Miyazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Suo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongfeng","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Haematology, National Clinical Research Centre for Blood Diseases, Institute of Haematology and Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Kirito","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology University of Yamanashi  Yamanashi 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