{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:07:05Z","timestamp":1791655625423,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    Model\u2010informed precision dosing (MIPD) of tacrolimus in renal allograft recipients, evaluated\n                    <jats:italic>in silico<\/jats:italic>\n                    , demonstrated improved (time to and) probability of target concentration attainment and smaller deviations from target range. Using simulated tacrolimus concentration\u2010time profiles, a study of 200 patients was predicted to have sufficient power to demonstrate superior performance of MIPD for these exposure end points compared with physician\u2010based dosing. A fully automated tacrolimus MIPD application integrated in the electronic patient file was tested in 293\n                    <jats:italic>de novo<\/jats:italic>\n                    recipients in the first 14\u2009days after transplantation in a prospective randomized controlled clinical validation study. More patients dosed with the MIPD application reached the primary study end point of three in\u2010target tacrolimus pre\u2010dose trough concentrations by Day 8, compared with physician\u2010dosed patients: 52.2% (95% CI: 45.3\u201359.6) vs. 35.7% (95% CI: 27.4\u201345.6); HR: 1.64 (95% CI: 1.10\u20132.43) (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015). The mean fraction of samples per patient in target during the complete study period was higher in the MIPD arm: 0.38\u2009\u00b1\u20090.14 compared with the physician\u2010dosed arm: 0.28\u2009\u00b1\u20090.14 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). The mean distance from target window was significantly lower in MIPD\u2010treated patients: 0.022 (95% CI: 0.019\u20130.024) vs. 0.040 (95% CI: 0.036\u20130.044) (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). On 19 occasions (&lt;\u20091%), MIPD tacrolimus dose suggestions were actively overruled by physicians. A fully automated MIPD application for tacrolimus in\n                    <jats:italic>de novo<\/jats:italic>\n                    renal recipients, integrated in the electronic patient file, demonstrated superior performance in achieving tacrolimus exposure targets with limited active overruling of MIPD dose executions by physicians. Automated MIPD can be tested in larger trials to evaluate the impact of dosing decision support on clinical outcomes after renal transplantation.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70090","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:44:18Z","timestamp":1760168658000},"page":"381-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Electronic Patient File\u2010Embedded Model\u2010Informed Precision Dosing Compared with Physician Dosing of Tacrolimus in Kidney Transplantation"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-9680","authenticated-orcid":false,"given":"Dirk R.J.","family":"Kuypers","sequence":"first","affiliation":[{"name":"Department of Nephrology and Renal Transplantation University Hospitals  Leuven Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-7351","authenticated-orcid":false,"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borefore","family":"Jallah","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation University Hospitals  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-0792","authenticated-orcid":false,"given":"Maarten","family":"Naesens","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation University Hospitals  Leuven Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxine","family":"Teuns","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation University Hospitals  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-442X","authenticated-orcid":false,"given":"Annouschka","family":"Laenen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-2443","authenticated-orcid":false,"given":"Ruben","family":"Faelens","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre KU Leuven  Leuven Belgium"},{"name":"Johnson &amp; Johnson, Clinical Pharmacology &amp; Pharmacometrics  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,11]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3460"},{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3510"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2049"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12758"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00922-x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01237-3"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2163"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13691"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000095"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14232"},{"key":"e_1_2_12_11_1","unstructured":"FaelensR LuyckxN LeirensQT. 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