{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:33:02Z","timestamp":1753878782836,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Transplantation"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD\u2010tac). Envarsus (LCP\u2010tac), an extended\u2010release formulation, is approved for adults but not for pediatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a pilot open\u2010label phase 1 study in stable pediatric kidney transplant recipients (age\u2009&lt;\u200918 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP\u2010tac versus BD\u2010tac. We conducted two 24\u2010h Pk studies: pre\u2010conversion (BD\u2010tac) and 4\u2009weeks post\u2010conversion to LCP\u2010tac. Patients were followed for 6 months, with the option to continue LCP\u2010tac.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five patients completed the study, with no returns to BD\u2010tac. Median age was 15\u2009years (range 11\u201317). LCP\u2010tac exhibited an extended\u2010release profile versus the bimodal profile of BD\u2010tac. Time to maximum concentration was delayed (5\u2009h vs. 1\u2009h), and maximum concentration was lower (9.9\u2009ng\/mL vs. 14.4\u2009ng\/mL). Tacrolimus area under the curve (24\u2009h) was comparable (141\u2009\u00b1\u200946.5\u2009ng\/mL vs. 164\u2009\u00b1\u200927.8\u2009ng\/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>, range\u2009\u2212\u20091.7 to 2.3\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>). Concentration\/dose ratio was higher in LCP\u2010tac (1.8\u2009\u00b1\u20090.64 vs. 0.8\u2009\u00b1\u20090.39). The final conversion ratio was 0.6 (BD\u2010tac: LCP\u2010tac).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our pilot study confirms the extended\u2010release Pk profile and improved absorption of LCP\u2010tac compared to BD\u2010tac. A larger study is needed to further evaluate the population Pk characteristics in children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/petr.14703","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:59:55Z","timestamp":1709528395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of Envarsus in pediatric kidney transplant recipients \u2013 phase 1 pilot conversion study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-8513","authenticated-orcid":false,"given":"Jon Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Paediatric Nephrology Nottingham University Hospitals NHS Trust  Nottingham UK"},{"name":"Department of Surgery University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Lawless","sequence":"additional","affiliation":[{"name":"Research and Innovation Nottingham University Hospitals NHS Trust  Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-6615","authenticated-orcid":false,"given":"David","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Wythenshawe Hospital  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9872-9243","authenticated-orcid":false,"given":"Andrew","family":"Maxted","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology Nottingham University Hospitals NHS Trust  Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-0750","authenticated-orcid":false,"given":"Andrew","family":"Lunn","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology Nottingham University Hospitals NHS Trust  Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meeta","family":"Mallik","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology Nottingham University Hospitals NHS Trust  Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alun","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology Nottingham University Hospitals NHS Trust  Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,3]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Emmes Corporation.Annual transplant report. 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