{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:48:23Z","timestamp":1788497303683,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T00:00:00Z","timestamp":1690070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001412 (Subaward PS\u2010Smith)"],"award-info":[{"award-number":["UL1TR001412 (Subaward PS\u2010Smith)"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R21DK077325"],"award-info":[{"award-number":["R21DK077325"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG056392"],"award-info":[{"award-number":["R01AG056392"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objective<\/jats:title><jats:p>The objective was to compare tacrolimus AUC<jats:sub>0\u201012<\/jats:sub> determined by Non\u2010Compartmental Analysis (NCA) using intensive sampling to <jats:italic>Maximum<\/jats:italic> a Posteriori<jats:italic>\u2010Bayesian (<\/jats:italic>MAP\u2010Bayesian<jats:italic>)<\/jats:italic> estimates from robust (<jats:italic>n<\/jats:italic>\u2009=\u20099 samples\/subject) and sparse (<jats:italic>n<\/jats:italic>\u2009=\u20092 samples\/subject) sampling in 67 stable KTRs and a validation group of similar patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This open\u2010label, prospective, single center 12\u2010h PK study included nine serial samples collected in KTRs to determine steady\u2010state NCA tacrolimus AUC<jats:sub>0\u201012<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>This study was conducted at a single site within a large, urban hospital in the western New York area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>This study described tacrolimus pharmacokinetics in stable kidney transplant recipients on maintenance tacrolimus therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Robust and sparse AUC<jats:sub>0\u201012<\/jats:sub> estimates by a MAP\u2010Bayesian approach were obtained using the Advanced Dosing Solutions (AdDS) and ADAPT5 freeware. Limited sampling strategies were evaluated using the original population PK model (<jats:italic>n<\/jats:italic>\u2009=\u200967), which was also assessed using a validation group (<jats:italic>n<\/jats:italic>\u2009=\u200915). AUC<jats:sub>0\u201012<\/jats:sub> agreement was tested by paired <jats:italic>t<\/jats:italic>\u2010tests with intraclass correlation coefficient (ICC) and Bland Altman analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>A total of 35 Black and 32 White stable KTRs (estimated glomerular filtration rate [eGFR]\u2009=\u200955.2\u2009\u00b1\u200915.7\u2009mL\/min\/1.73m<jats:sup>2<\/jats:sup>) received the tacrolimus dose of 3.4\u2009\u00b1\u20091.7\u2009mg\/study with troughs of 6.8\u2009\u00b1\u20091.8\u2009ng\/mL. The NCA\u2010AUC<jats:sub>0\u201012<\/jats:sub> was 123.8\u2009\u00b1\u200933.6\u2009\u03bcg\u00b7h\/L compared to MAP\u2010Bayesian estimates for Robust\u2010AUC<jats:sub>0\u201012<\/jats:sub> of 124.7\u2009\u00b1\u200933.3\u2009\u03bcg\u00b7h\/L and optimal 2\u2010specimen Sparse\u2010AUC<jats:sub>0\u201012<\/jats:sub> of 119.7\u2009\u00b1\u200932.7\u2009\u03bcg\u00b7h\/L for the training group. Comparison of Robust\u2010AUC<jats:sub>0\u201012<\/jats:sub> to NCA\u2010AUC<jats:sub>0\u201012<\/jats:sub> had an ICC of 0.96 (<jats:italic>p<\/jats:italic>\u2009=\u20090.99) while comparison of Robust\u2010AUC<jats:sub>0\u201012<\/jats:sub> to Sparse\u2010AUC<jats:sub>0\u201012<\/jats:sub> using Pre\u2010dose trough [C(t<jats:sub>0h<\/jats:sub>)] and 1\u2009h [C(t<jats:sub>1h<\/jats:sub>)] resulted in an ICC of 0.93 (<jats:italic>p<\/jats:italic>\u2009=\u20090.014). In the validation group, 5 Black and 10 White KTRs (eGFR\u2009=\u200956.4\u2009\u00b1\u200916.8\u2009mL\/min\/1.73m<jats:sup>2<\/jats:sup>) received a mean tacrolimus dose of 1.9\u2009\u00b1\u20091.2\u2009mg\/study with a trough of 6.0\u2009\u00b1\u20091.7\u2009ng\/mL. The validation group's NCA\u2010AUC<jats:sub>0\u201012<\/jats:sub> (88.4\u2009\u00b1\u200933.1\u2009\u03bcg\u00b7h\/L) was comparable to Robust\u2010AUC<jats:sub>0\u201012<\/jats:sub> (85.1\u2009\u00b1\u200933.8\u2009\u03bcg\u00b7h\/L, ICC\u2009=\u20090.93; <jats:italic>p<\/jats:italic>\u2009=\u20090.12) and Sparse\u2010AUC<jats:sub>0\u201012<\/jats:sub> determined from C(t<jats:sub>0h<\/jats:sub>) and C(t<jats:sub>4h<\/jats:sub>) (86.7\u2009\u00b1\u200933.9\u2009\u03bcg\u00b7h\/L, ICC\u2009=\u20090.91; <jats:italic>p<\/jats:italic>\u2009=\u20090.61).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MAP\u2010Bayesian estimation for patient\u2010specific AUC<jats:sub>0\u201012<\/jats:sub> using sparse, two\u2010specimen sampling is comparable to NCA and may enhance tacrolimus TDM in stable KTRs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2848","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T04:38:20Z","timestamp":1689395900000},"page":"1032-1042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bayesian optimization of tacrolimus exposure in stable kidney transplant patients"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1069-1720","authenticated-orcid":false,"given":"Thomas D.","family":"Nguyen","sequence":"first","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences University at Buffalo Buffalo New York USA"},{"name":"New York State Center for Excellence in Bioinformatics and Life Sciences Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-2787","authenticated-orcid":false,"given":"Nicholas M.","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences University at Buffalo Buffalo New York USA"},{"name":"New York State Center for Excellence in Bioinformatics and Life Sciences Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-5472","authenticated-orcid":false,"given":"Kris","family":"Attwood","sequence":"additional","affiliation":[{"name":"Biostatistics School of Public Health and Health Professions Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijaz","family":"Gundroo","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA"},{"name":"Erie County Medical Center Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahfuz","family":"Yonis","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA"},{"name":"Erie County Medical Center Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA"},{"name":"Erie County Medical Center Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2028-4998","authenticated-orcid":false,"given":"Kathleen M.","family":"Tornatore","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences University at Buffalo Buffalo New York USA"},{"name":"Division of Nephrology Department of Medicine Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,23]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"21","article-title":"Annual data report: kidney","volume":"2021","author":"Hart A","year":"2019","journal-title":"Am J Transplant"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000640"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181a23cb2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2656"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13811"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1118"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000503"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0396-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000814"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01060893"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2631"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.142"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920111798808428"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12410"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199529060-00003"},{"key":"e_1_2_9_17_1","volume-title":"User's Guide: Pharmacokinetic\/Pharmacodynamic Systems Analysis Software","author":"D'Argenio DZ","year":"2009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e318285e779"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02834.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03791106"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.12.009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.9.1905"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2017.1395413"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.07.029"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00352.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000158080.61201.65"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03815.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318080-000000000-00000"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31820f40f8"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.02.004"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01070904"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2848","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:37:40Z","timestamp":1761061060000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,23]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/phar.2848"],"URL":"https:\/\/doi.org\/10.1002\/phar.2848","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,23]]},"assertion":[{"value":"2022-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}