{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:04:06Z","timestamp":1789700646703,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tacrolimus dosing in liver transplantation is complicated by a narrow therapeutic index and high\n                    <jats:italic>CYP3A5<\/jats:italic>\n                    genetic variability. While saturable Michaelis\u2013Menten kinetics can explain nonlinearities, identifying saturable parameters from routine clinical data remains challenging. This study aimed to determine the optimal structural model and develop a precision dosing algorithm. A population pharmacokinetic analysis was conducted in 114 patients, yielding 1989 observations.\n                    <jats:italic>CYP3A5<\/jats:italic>\n                    genotypes were determined for both recipients and donors. Using Phoenix NLME, we rigorously compared linear versus Michaelis\u2013Menten elimination structures. Stepwise covariate modeling was conducted to quantify the impact of genetic, physiological, and pharmacological factors, followed by Monte Carlo simulations to optimize dosing. A conventional two\u2010compartment model adequately described the data without requiring a Michaelis\u2013Menten structure. The combined\n                    <jats:italic>CYP3A5<\/jats:italic>\n                    genotype exhibited a distinct stepwise reduction in apparent clearance from the homozygous expressor to the non\u2010expressor group. Fluconazole emerged as a major inhibitor, reducing clearance by 33%, whereas prednisolone showed modest induction. Hemoglobin displayed a significant inverse relationship with clearance. Crucially, incorporating the daily dose as a covariate on clearance effectively captured the apparent nonlinear disposition. Simulations confirmed that fluconazole\u2010treated patients require substantially lower doses (1.5\u20133.0\u2009mg every 12\u2009h) compared with fluconazole\u2010free patients (2.5\u20137.0\u2009mg every 12\u2009h). A dose\u2010dependent two\u2010compartment model offers a basis for model\u2010informed dose selection, addressing reported nonlinearities through physiological covariates. We provide a model\u2010informed dosing algorithm that accounts for combined recipient\/donor genetics and drug interactions, which may improve target attainment in liver transplant populations.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70339","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:04:51Z","timestamp":1788419091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor\u2010Recipient\n                    <i>CYP3A5<\/i>\n                    Pharmacogenomics and Drug Interactions"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8711-2752","authenticated-orcid":false,"given":"Virunya","family":"Komenkul","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"},{"name":"Department of Pharmaceutical Care, Faculty of Pharmacy Silpakorn University  Nakorn Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5533-5698","authenticated-orcid":false,"given":"Prawat","family":"Chantharit","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1357-9547","authenticated-orcid":false,"given":"Piyawat","family":"Komolmit","sequence":"additional","affiliation":[{"name":"Excellence Center in Liver Diseases King Chulalongkorn Memorial Hospital, Thai Red Cross Society  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bunthoon","family":"Nonthasoot","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Chulalongkorn University &amp; King Chulalongkorn Memorial Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-1895","authenticated-orcid":false,"given":"Athaya","family":"Vorasittha","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Chulalongkorn University &amp; King Chulalongkorn Memorial Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-3379","authenticated-orcid":false,"given":"Anapat","family":"Sanpavat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-3245","authenticated-orcid":false,"given":"Sirinporn","family":"Suksawatamnuay","sequence":"additional","affiliation":[{"name":"Excellence Center in Liver Diseases King Chulalongkorn Memorial Hospital, Thai Red Cross Society  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-5387","authenticated-orcid":false,"given":"Chandramouli","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Certara  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1474-4249","authenticated-orcid":false,"given":"Thitima","family":"Wattanavijitkul","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160421"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01360.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2021.100610"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13276"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443100-00001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199529060-00003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.113"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2021.10.031"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280100331"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.8.1069"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31824a67eb"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12599"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S184376"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.110"},{"key":"e_1_2_9_16_1","article-title":"The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Llver Transplantation Patients","volume":"2014","author":"Zhu L.","year":"2014","journal-title":"Journal of Pharmacy"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2022.2073851"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.971"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028019897050"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2311"},{"key":"e_1_2_9_21_1","first-page":"17","article-title":"Population Pharmacokinetics of Tacrolimus in Thai Liver Transplant Patients","volume":"16","author":"Tharanon V.","year":"2021","journal-title":"Thai Bulletin of Pharmaceutical Sciences"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2156"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-024-03692-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105237"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1031969"},{"key":"e_1_2_9_26_1","volume-title":"Thai Transplant Care (TTC) Liver","author":"Society, T.T","year":"2022"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4557-0268-8.00091-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqae005"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2008.04.005"},{"key":"e_1_2_9_30_1","article-title":"Preparation of Formalin\u2010Fixed Paraffin\u2010Embedded Tissue Cores for Both RNA and DNA Extraction","volume":"114","author":"Patel P. 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