{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:39:03Z","timestamp":1792993143204,"version":"4.5.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tacrolimus is a first\u2010line immunosuppressant used to prevent rejection in living donor liver transplantation (LDLT) and is subject to therapeutic drug monitoring due to its concentration\u2010dependent effects and side effects. Metabolism of tacrolimus is reduced by the CYP3A5*3 allele. In addition, liver regeneration over time leads to increased tacrolimus clearance. The purpose of this study was to develop a tacrolimus population pharmacokinetic (popPK) model that takes into consideration the CYP3A5*3 allele and the time\u2010dependent increase in clearance. To develop the popPK model, we used data from 25 recipients and 25 donors who received LDLT and tacrolimus at Kumamoto University Hospital. The measured data consisted of four blood concentration points including peak values at 12\u00a0h after the first dose of tacrolimus, and trough blood concentrations obtained by TDM on consecutive days. Nonlinear mixed\u2010effects modeling method was used to develop the popPK model, and i\u2010Densy by ARKRAY Co., Ltd. was used for CYP3A5 gene polymorphism analysis. The popPK model was developed as a one\u2010compartment model incorporating a time\u2010dependent sigmoidal model for clearance. Total bilirubin value was found to be a predictor of volume of distribution and rate constant of absorption, while aspartate transaminase was found to be a predictor of volume of distribution. The CYP3A5*3 allele was not found to be a predictor of tacrolimus pharmacokinetics. We developed a popPK model that includes a time\u2010dependent increase in CL of tacrolimus for patients with LDLT.<\/jats:p>","DOI":"10.1002\/jcph.70315","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:18:56Z","timestamp":1792671536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Analysis of Tacrolimus in Time\u2010Dependent Increase of Clearance for Patients with Living\u2010Donor Liver Transplantation: A Prospective Observational Study"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8275-3195","authenticated-orcid":false,"given":"Naoya","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmaceutical Sciences Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0693-1896","authenticated-orcid":false,"given":"Kazutaka","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Shimata","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Transplantation Kumamoto University Graduate School of Medical Sciences  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Hirukawa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Transplantation Kumamoto University Graduate School of Medical Sciences  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Transplantation Kumamoto University Graduate School of Medical Sciences  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-228X","authenticated-orcid":false,"given":"Taizo","family":"Hibi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Transplantation Kumamoto University Graduate School of Medical Sciences  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-7597","authenticated-orcid":false,"given":"Hirofumi","family":"Jono","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmaceutical Sciences Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Pharmacy Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmaceutical Sciences Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Pharmacy Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2011.03616.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200443100\u201000001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra065156"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1325"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.22.328"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318200e971"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010002\u20100499\u20105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.06.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12420"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280100331"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12599"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028019897050"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2156"},{"key":"e_1_2_9_15_1","article-title":"The population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients","volume":"2014","author":"Zhu L","year":"2014","journal-title":"J Pharm"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S184376"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001201"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2008.03162.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.690"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122009999"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70315","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70315","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:32:28Z","timestamp":1792992748000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jcph.70315"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70315","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70315"}}