{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:25:05Z","timestamp":1789781105453,"version":"4.0.1"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence\u2010based guidelines for CYP3A5 normal\/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive <jats:italic>CYP3A<\/jats:italic> genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for <jats:italic>CYP3A5<\/jats:italic> and <jats:italic>CYP3A4<\/jats:italic> was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic\u2010recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third\u2010party payers. CYP3A5 normal\/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only \u224866% of African Americans in our cohort were normal\/intermediate metabolizers who required higher doses. Routine <jats:italic>CYP3A5<\/jats:italic> genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.<\/jats:p>","DOI":"10.1002\/jcph.2249","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T09:24:23Z","timestamp":1681291463000},"page":"961-967","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-9811","authenticated-orcid":false,"given":"Emma","family":"Tillman","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miley G.","family":"Nikirk","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Indiana University Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Indiana University Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd C.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Shugg","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith P.","family":"Maddatu","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif A.","family":"Sharfuddin","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Eadon","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Indiana University Health  Indianapolis Indiana USA"},{"name":"Division of Nephrology Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13666"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.38"},{"key":"e_1_2_8_4_1","volume-title":"Package Insert","author":"Tacrolimus","year":"2021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102154"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02389.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.10.008"},{"issue":"12","key":"e_1_2_8_8_1","first-page":"1315","article-title":"Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability","volume":"23","author":"Lampen A","year":"1995","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.113"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.377"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200211270-00005"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2022.03.008"},{"key":"e_1_2_8_13_1","unstructured":"BioRender. 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