{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:26:45Z","timestamp":1793395605735,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tacrolimus, the most common immunosuppressant for organ transplant, has a narrow therapeutic range and is metabolized by CYP3A4\/5. Trough concentration monitoring and dosing adjustments are used to reach a therapeutic range. CYP3A5 intermediate and normal metabolizers (*1 allele carriers; IM\/NM) demonstrate faster tacrolimus metabolism than poor metabolizers (PM). We analyzed the electronic health records of 93 patients aged\u2009&lt;21\u2009years for the first 8\u2009weeks after a kidney transplant between January 2010 and December 2021. The target tacrolimus trough was 10\u201315\u2009ng\/mL in the first 4\u2009weeks and 7\u201310\u2009ng\/mL in the next 4\u2009weeks. Banked DNA was collected and genotyped for CYP3A5*3, *6, *7, and *8 alleles. We found that CYP3A5 IM\/NM (<jats:italic>n<\/jats:italic>\u2009=\u200921) took longer than PM (<jats:italic>n<\/jats:italic>\u2009=\u200972) to reach the therapeutic range (7 vs. 4\u2009days, <jats:italic>p<\/jats:italic>\u2009=\u20090.048). IM\/NM had more dose adjustments (8 vs. 6, <jats:italic>p<\/jats:italic>\u2009=\u20090.025) and needed &gt;150% of the required daily dose compared with PM. The concentration\/dose ratio was influenced by age and concomitant fluconazole (<jats:italic>p<\/jats:italic>\u2009=\u20090.0003, <jats:italic>p<\/jats:italic>\u2009=\u20090.034, respectively) and the average daily dose decreases with age in CYP3A5 PM (<jats:italic>p<\/jats:italic>\u2009=\u20090.001). Tremors were more common in patients who ever had a trough concentration\u2009&gt;15\u2009ng\/mL compared with those who never had a trough concentration\u2009&gt;15\u2009ng\/mL (OR 3.31, 95% CI 1.03\u20138.98, <jats:italic>p<\/jats:italic>\u2009=\u20090.038). Using standard dosing, CYP3A5 IM\/NM took longer to reach the goal range and require more dose adjustments and higher doses than PM. Preemptive genotyping could decrease the number of dose changes necessary to reach a therapeutic dose. We have implemented pre\u2010transplant CYP3A5 testing at our institution.<\/jats:p>","DOI":"10.1111\/cts.13571","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T06:08:56Z","timestamp":1687327736000},"page":"1768-1778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tacrolimus pharmacokinetics are influenced by <scp>CYP3A5<\/scp>, age, and concomitant fluconazole in pediatric kidney transplant patients"],"prefix":"10.1111","volume":"16","author":[{"given":"Alaa","family":"Alghamdi","sequence":"first","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"College of Clinical Pharmacy Imam Abdulrahman Bin Faisal University  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Seay","sequence":"additional","affiliation":[{"name":"Department of Chemistry Virginia Tech Center for Drug Discovery  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-4291","authenticated-orcid":false,"given":"David K.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Nephrology &amp; Hypertension, James M. Anderson Center fo Health Systems Excellence Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles D.","family":"Varnell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Nephrology &amp; Hypertension, James M. 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