{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:27:21Z","timestamp":1788582441385,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Interpatient variability in tacrolimus pharmacokinetics is due in part to variation in metabolism by cytochrome P\u2010450 3A5 and 3A4 and membrane transport by P\u2010glycoprotein. We evaluated the combined role\n                    <jats:italic>CYP3A5*3<\/jats:italic>\n                    and\n                    <jats:italic>CYP3A4*1B<\/jats:italic>\n                    genotypes have on tacrolimus pharmacokinetics in 65 stable Black and White kidney transplant recipients receiving maintenance immunosuppression of tacrolimus and mycophenolic acid. Tacrolimus apparent clearance, trough (C\n                    <jats:sub>12h<\/jats:sub>\n                    ), C\n                    <jats:sub>12h<\/jats:sub>\n                    \/Dose, AUC\n                    <jats:sub>0\u201312<\/jats:sub>\n                    , and AUC\n                    <jats:sub>0\u201312<\/jats:sub>\n                    \/Dose as well as\n                    <jats:italic>CYP3A5 *3<\/jats:italic>\n                    (rs776746) variants responsible for loss of protein function and\n                    <jats:italic>CYP3A4\u20101B<\/jats:italic>\n                    (\n                    <jats:italic>rs2740574<\/jats:italic>\n                    ) associated with increased CYP3A4 function were assessed. To investigate the association of tacrolimus pharmacokinetics with the\n                    <jats:italic>CYP3A5 *3<\/jats:italic>\n                    and\n                    <jats:italic>CYP3A4*1B<\/jats:italic>\n                    genotypes, we created a metabolic composite to classify patients as Extensive, Intermediate, and Poor Metabolizers on the basis of the relative expression of specific combinations of\n                    <jats:italic>CYP3A5 *3<\/jats:italic>\n                    and\n                    <jats:italic>CYP3A4*1B<\/jats:italic>\n                    genotypes. The incorporation of\n                    <jats:italic>CYP3A5*3<\/jats:italic>\n                    and\n                    <jats:italic>CYP3A4*1B<\/jats:italic>\n                    genotypes that investigate the role of these composite genotypic variants on tacrolimus pharmacokinetics provides additional insights into targeted tacrolimus dosing regimens in these sub\u2010populations. The Extensive Metabolic Composite had twice the dose and toughs when compared to the Poor composite. Approximately 88% of Blacks were classified as Extensive or Intermediate Metabolizers requiring higher tacrolimus doses to accommodate the more rapid clearance. The remaining Blacks exhibited loss of function SNPs associated with lower tacrolimus doses comparable to Whites. This is the first report describing the association of\n                    <jats:italic>CYP3A5*3 and CYP3A4\u20101B<\/jats:italic>\n                    Metabolic Composites on tacrolimus pharmacokinetics in Black and White kidney transplant recipients and provides insight into the interpatient pharmacokinetic variability of this key immunosuppressive drug.\n                  <\/jats:p>","DOI":"10.1111\/cts.70370","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:58:12Z","timestamp":1760407092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of Metabolic Genotype Composite\n                    <i>CYP3A5*3<\/i>\n                    and\n                    <i>CYP3A4*1B<\/i>\n                    to Tacrolimus Pharmacokinetics in Stable Black and White Kidney Transplant Recipients"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0281-3908","authenticated-orcid":false,"given":"Daniel","family":"Brazeau","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy; Marshall University  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-5472","authenticated-orcid":false,"given":"Kristopher","family":"Attwood","sequence":"additional","affiliation":[{"name":"Biostatistics School of Public Health and Health Professions  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-3972","authenticated-orcid":false,"given":"Louse M.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Immunosuppressive Pharmacology Research Program, Clinical and Translational Therapeutics School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Gray","sequence":"additional","affiliation":[{"name":"Immunosuppressive Pharmacology Research Program, Clinical and Translational Therapeutics School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-5314","authenticated-orcid":false,"given":"Shirley","family":"Chang","sequence":"additional","affiliation":[{"name":"Nephrology Division; Medicine School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Chen","sequence":"additional","affiliation":[{"name":"Immunosuppressive Pharmacology Research Program, Clinical and Translational Therapeutics School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7917-8893","authenticated-orcid":false,"given":"Brian M.","family":"Murray","sequence":"additional","affiliation":[{"name":"Nephrology Division; Medicine School of Medicine and Biomedical Sciences University at Buffalo  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":"Immunosuppressive Pharmacology Research Program, Clinical and Translational Therapeutics School of Pharmacy and Pharmaceutical Sciences  Buffalo New York USA"},{"name":"Nephrology Division; Medicine School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13195"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03791106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3181aa36cd"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2016.1151037"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12798"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000640"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2015.01.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12191"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317550\u2010000000000\u201000000"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317350\u2010000000000\u201000000"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2013.05.033"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2005.01118.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200202000-00007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011233432107"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2005.05.002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2007.01.024"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2009.03009.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.02.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs\u20102016\u20100136"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2011.03974.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199802270-00011"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000259248.60448.8a"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.113183"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.4.413"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.128388"},{"key":"e_1_2_10_28_1","first-page":"1","article-title":"Race and Sex Associations With Tacrolimus Pharmacokinetics in Stable Renal Transplant Recipients","volume":"00","author":"Tornatore K. 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