biostudies-literatureUnknownHernandez S<i>CYP3A5</i> genetic variants are associated with tacrolimus metabolism. Controversy remains on whether <i>CYP3A4</i> increased [* <i>1B</i> (rs2740574), <i>*1G</i> (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*7Bor *7G variants (Group 3) compared to <i>CYP3A4*1/*1</i> (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.Research squarers.3.rs-2921796https://www.ebi.ac.uk/biostudies/studies/S-EPMC10246090biostudies-literatureComposite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients.PMC10246090Aquilante CVan Driest SLindenfeld JLiu MDeininger KHernandez SSchlendorf KfalseComposite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients.<i>CYP3A5</i> genetic variants are associated with tacrolimus metabolism. Controversy remains on whether <i>CYP3A4</i> increased [* <i>1B</i> (rs2740574), <i>*1G</i> (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*7Bor *7G variants (Group 3) compared to <i>CYP3A4*1/*1</i> (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.2023-01-01T00:00:00Z2023 May2025-04-04T10:21:50.072Z2025-02-19T02:38:03.721ZS-EPMC102460903729289310.21203/rs.3.rs-2921796/v1