{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:16:36Z","timestamp":1776816996826,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K\/AkT\/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC\/MS2 analysis, was used to develop a population pharmacokinetic model (Monolix\u00ae software). A mono-compartmental model with first-order absorption and elimination best fit the data. The only covariate retained for the final model was \u201cbody surface area\u201d (D1 and D8). The model also demonstrated that 1.5 mg\/m2 would be the recommended sirolimus dose for further studies and that steady-state TDM is necessary to adjust the dosing regimen in atypical profiles (36.4% of the population). No correlation was found between sirolimus trough concentrations and efficacy and\/or observed toxicities. The study reveals the relevance of sirolimus TDM in pediatric oncology as it is needed in organ transplantation.<\/jats:p>","DOI":"10.3390\/pharmaceutics13040470","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology"],"prefix":"10.3390","volume":"13","author":[{"given":"Amelia-Naomi","family":"Sabo","sequence":"first","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"},{"name":"Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unit\u00e9 de Recherche 7296, Facult\u00e9 de M\u00e9decine de Ma\u00efeutique et des M\u00e9tiers de la Sant\u00e9, Centre de Recherche en Biom\u00e9decine de Strasbourg (CRBS), 67085 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-2473","authenticated-orcid":false,"given":"Sarah","family":"Jannier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Onco-H\u00e9matologie P\u00e9diatrique, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Becker","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unit\u00e9 de Recherche 7296, Facult\u00e9 de M\u00e9decine de Ma\u00efeutique et des M\u00e9tiers de la Sant\u00e9, Centre de Recherche en Biom\u00e9decine de Strasbourg (CRBS), 67085 Strasbourg, France"},{"name":"Service de la Pharmacie, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Marc","family":"Lessinger","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natacha","family":"Entz-Werl\u00e9","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Onco-H\u00e9matologie P\u00e9diatrique, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) 7021, Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioimagerie et Pathologies, Signalisation Tumorale et Cibles Th\u00e9rapeutiques, Facult\u00e9 de Pharmacie, Universit\u00e9 de Strasbourg, 67401 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-4293","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Kemmel","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pitaux Universitaires de Strasbourg, 67200 Strasbourg, France"},{"name":"Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unit\u00e9 de Recherche 7296, Facult\u00e9 de M\u00e9decine de Ma\u00efeutique et des M\u00e9tiers de la Sant\u00e9, Centre de Recherche en Biom\u00e9decine de Strasbourg (CRBS), 67085 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/ndt\/gfi336","article-title":"Conversion from Calcineurin Inhibitors to Sirolimus in Chronic Allograft Nephropathy: Benefits and Risks","volume":"21","author":"Diekmann","year":"2006","journal-title":"Nephrol. 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