{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:01:38Z","timestamp":1773036098398,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tacrolimus is primarily metabolized by Cytochrome P450 (CYP)3A4\/5. The Clinical Pharmacogenetics Implementation Consortium recommends increasing the initial dose 1.5\u2010 to 2\u2010fold in CYP3A5 expressers to enhance transplant outcomes. Our objective was to investigate the impact of CYP3A5 expresser status on tacrolimus dosing requirements and attainment of target trough concentrations in heart transplant recipients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a retrospective cohort analysis of tacrolimus dose, concentration, demographics, CYP3A4\/5 genotype, concomitant medications, and biochemical data in heart transplant recipients from December 2020 to August 2023. The primary outcome was the time to first therapeutic trough concentration, compared by CYP3A5 expression status. Secondary outcomes included the tacrolimus dose at target trough and dose\u2010adjusted tacrolimus trough concentration (C\n                      <jats:sub>0<\/jats:sub>\n                      \/D). Stepwise multiple regression was performed to account for potential covariates. Moreover, clinical outcomes were assessed at 1\u2010year post\u2010transplantation and compared based on CYP3A5 expression status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 33 patients, CYP3A5 expressers (27.3%) required longer to achieve therapeutic trough concentrations (median [Q1, Q3]: expressers: 14 [9.5, 16] days vs. nonexpressers 7.5 [6.0, 11] days;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0073) and required nearly double the tacrolimus dose to reach target concentrations (10 [5.5, 13] mg\/day for expressers vs. 5 [3.3, 5.9] mg\/day for nonexpressers;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0019). Conversely, the C\n                      <jats:sub>0<\/jats:sub>\n                      \/D was nearly 2\u2010fold higher in nonexpressers 2.0 [1.6, 3.4] ng\/(mL*mg) than expressers (1.1 [0.83, 1.7] ng\/(mL*mg);\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0015). Stepwise regression identified route of administration (sublingual vs. oral) at therapeutic trough and initial dose as covariates for all outcomes. All clinical outcomes showed no significant differences based on CYP3A5 expression status, with the exception that poor metabolizers demonstrated higher serum creatinine elevation at 1\u2010week post\u2010transplantation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.047).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings highlight the impact of CYP3A5 expresser status on the time needed and dosing requirements to attain tacrolimus therapeutic concentrations in heart transplant recipients, suggesting\n                      <jats:italic>CYP3A5<\/jats:italic>\n                      \u2010guided dosing strategies may improve rapid attainment of therapeutic tacrolimus concentrations.\n                    <\/jats:p>\n                  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