{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:32:14Z","timestamp":1769783534113,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A670732"],"award-info":[{"award-number":["N42A670732"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Patients with transfusion\u2010dependent thalassemia (TDT) require lifelong blood transfusions, resulting in excessive iron accumulation and necessitating effective chelation therapy. Deferasirox (DFX) is the primary oral iron chelator for managing iron overload; however, the response to this treatment varies substantially within different individuals, potentially because of differences in its pharmacokinetics (PK) and pharmacodynamics (PD). This study aimed to develop a physiologically based pharmacokinetic\u2013pharmacodynamic (PBPK\/PD) DFX model, integrating hepatic\u2010 and transfusion\u2010derived iron burdens to assess their impact on DFX PK and optimize dosing. The model was developed using clinical PK data from Caucasian and Thai populations, comprising healthy individuals and patients with TDT. TDT\u2010specific physiological parameters were incorporated into the TDT model. The verified model was applied to predict the targeted DFX dose required to achieve a 25% reduction in the liver iron concentration (LIC) from baseline after 6\u2009months of treatment based on the baseline LIC and blood transfusion regimen. The model demonstrated high predictive accuracy across populations, identifying the effects of iron levels on DFX clearance. Simulations revealed that patients with higher baseline LIC were more likely to achieve the targeted reduction, whereas those with lower LIC required higher doses because of slower iron mobilization. A reduced blood transfusion regimen was associated with improved therapeutic outcomes at the same DFX dose. The PBPK\/PD model proposed targeted DFX doses to achieve a 25% reduction based on baseline LIC levels and transfusion regimen, emphasizing the requirement for individualized dosing strategies based on iron burden and blood transfusion patterns to maximize clinical outcomes.<\/jats:p>","DOI":"10.1111\/cts.70355","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T13:43:56Z","timestamp":1758203036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bridging Pharmacokinetics and Pharmacodynamics: A\n                    <scp>PBPK<\/scp>\n                    \/\n                    <scp>PD<\/scp>\n                    Model\u2010Based Approach for Deferasirox Dosing in Transfusion\u2010Dependent Thalassemia"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-2646","authenticated-orcid":false,"given":"Watchara","family":"Sakares","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Faculty of Pharmaceutical Sciences, Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-9406","authenticated-orcid":false,"given":"Udomsak","family":"Udomnilobol","sequence":"additional","affiliation":[{"name":"Chulalongkorn University Drug Discovery and Drug Development Research Center (Chula4DR) Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2418-5970","authenticated-orcid":false,"given":"Xian","family":"Pan","sequence":"additional","affiliation":[{"name":"Certara Predictive Technologies Division Certara UK Limited  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7653-7101","authenticated-orcid":false,"given":"Kittika","family":"Yampayon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Faculty of Pharmaceutical Sciences, Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-595X","authenticated-orcid":false,"given":"Supachai","family":"Ekwattanakit","sequence":"additional","affiliation":[{"name":"Siriraj Thalassemia Center Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3162-1849","authenticated-orcid":false,"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Siriraj Thalassemia Center Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"},{"name":"Division of Hematology\/Oncology, Department of Pediatrics Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7374-6765","authenticated-orcid":false,"given":"Chanin","family":"Limwongse","sequence":"additional","affiliation":[{"name":"Siriraj Thalassemia Center Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"},{"name":"Siriraj Genomics Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8781","authenticated-orcid":false,"given":"Somdet","family":"Srichairatanakool","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine, Chiang Mai University  Chiang Mai 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in Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31822\u20106"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426\u2010200011000\u201000024"},{"key":"e_1_2_9_4_1","volume-title":"Clinical Practice Guidelines for Diagnosis and Management of Thalassemia Syndromes (In Thai)","author":"Fucharoen 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Pharmaceuticals \u201cEXJADE (Deferasirox) US Prescribing Information \u201d accessed May 6 2024 https:\/\/www.novartis.com\/us\u2010en\/sites\/novartis_us\/files\/exjade.pdf."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2016.02.006"},{"key":"e_1_2_9_26_1","unstructured":"E.Akoy B.Suman andB.Kanik \u201cSoluble and Dispersible Pharmaceutical Deferasirox Formulation \u201d Patent No. WO 2016\/028245 A1 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