{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:44:31Z","timestamp":1785411871725,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,11]],"date-time":"2016-07-11T00:00:00Z","timestamp":1468195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["12GRNT12040211"],"award-info":[{"award-number":["12GRNT12040211"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005508","name":"Boettcher Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005508","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2016,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Cytochrome P450 (CYP<\/jats:styled-content><\/jats:italic>) 3A<\/jats:italic> polymorphisms are associated with variable CYP<\/jats:styled-content>3A metabolizing enzyme activity and tacrolimus pharmacokinetics. We sought to determine the singular and combined impact of CYP<\/jats:styled-content>3A4*22<\/jats:italic> and CYP<\/jats:styled-content>3A5*3<\/jats:italic> variants on tacrolimus drug disposition in adult heart transplant recipients.<\/jats:p><\/jats:sec>Methods<\/jats:title>The retrospective study included 76 patients greater than one year post\u2010heart transplant and receiving tacrolimus. Patients were genotyped for CYP<\/jats:styled-content>3A4*22<\/jats:italic> and CYP<\/jats:styled-content>3A5*3<\/jats:italic>, and combined genotypes were classified as follows: extensive metabolizers (EM<\/jats:styled-content>, CYP<\/jats:styled-content>3A4*1\/*1<\/jats:italic>+CYP<\/jats:styled-content>3A5*1<\/jats:italic> carriers), intermediate metabolizers (IM<\/jats:styled-content>, CYP<\/jats:styled-content>3A4*1\/*1<\/jats:italic>+CYP<\/jats:styled-content>3A5*3\/*3<\/jats:italic>, or CYP<\/jats:styled-content>3A4*22<\/jats:italic> carriers+CYP<\/jats:styled-content>3A5*1<\/jats:italic> carriers), and poor metabolizers (PM<\/jats:styled-content>, CYP<\/jats:styled-content>3A4*22<\/jats:italic> carriers+CYP<\/jats:styled-content>3A5*3\/*3<\/jats:italic>). The primary outcome was tacrolimus dose\u2010adjusted trough concentration (C0<\/jats:sub>\/D, ng\/mL<\/jats:styled-content> per mg\/d).<\/jats:p><\/jats:sec>Results<\/jats:title>In singular analysis, tacrolimus C0<\/jats:sub>\/D did not differ significantly between CYP<\/jats:styled-content>3A4*22<\/jats:italic> genotype groups. However, tacrolimus C0<\/jats:sub>\/D was 1.8\u2010fold lower (P<\/jats:italic><.001) in CYP<\/jats:styled-content>3A5 expressers vs non\u2010expressers. When combined CYP<\/jats:styled-content>3A<\/jats:italic> genotypes were evaluated, tacrolimus C0<\/jats:sub>\/D was 1.8\u2010fold lower in EM<\/jats:styled-content>s vs IM<\/jats:styled-content>s (P<\/jats:italic><.001) and EM<\/jats:styled-content>s vs PM<\/jats:styled-content>s (P<\/jats:italic>=.001). Tacrolimus C0<\/jats:sub>\/D did not differ significantly between CYP<\/jats:styled-content>3A IM<\/jats:styled-content>s vs PM<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Combined CYP<\/jats:styled-content>3A<\/jats:italic> genotype was associated with tacrolimus drug disposition in adult heart transplant recipients, but the effect was largely driven by CYP<\/jats:styled-content>3A5*3<\/jats:italic>. These data suggest that CYP<\/jats:styled-content>3A4*22<\/jats:italic> and combined CYP<\/jats:styled-content>3A<\/jats:italic> genotypes are unlikely to provide additional information beyond CYP<\/jats:styled-content>3A5<\/jats:italic> genotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.12790","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T13:40:30Z","timestamp":1466170830000},"page":"1074-1081","source":"Crossref","is-referenced-by-count":31,"title":["CYP<\/scp>3A<\/i> pharmacogenetics and tacrolimus disposition in adult heart transplant recipients"],"prefix":"10.1111","volume":"30","author":[{"given":"Kimberly M.","family":"Deininger","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Robert L.","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrut V.","family":"Ambardekar","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Colorado School of Medicine Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Lindenfeld","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Cardiac Transplant Program Vanderbilt Heart and Vascular 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