{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:18:00Z","timestamp":1771334280343,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"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":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Selpercatinib is a first\u2010in\u2010class, highly selective, RET kinase inhibitor with CNS activity, approved for the treatment of RET\u2010altered lung, thyroid, and other cancers. We report pharmacokinetic analyses to identify factors affecting selpercatinib steady\u2010state exposure and support posology in pediatric patients. Population pharmacokinetic analyses using nonlinear mixed\u2010effects modeling were performed on data from two ongoing, open\u2010label, Phase 1\/2 studies in adult and pediatric patients with advanced solid tumors. In LIBRETTO\u2010001 (NCT03157128) patients (\u2265\u200912\u2009years) received oral selpercatinib from 20\u2009mg once daily through 240\u2009mg twice daily (BID) during phase 1 and 160\u2009mg BID in phase 2. In LIBRETTO\u2010121 (NCT03899792), patients (6\u2009months\u201321\u2009years) received doses based on body surface area (BSA), starting at a dose expected to match adult exposure of 160\u2009mg BID. Overall, 8024 selpercatinib plasma concentration measurements from 830 patients were included in the pharmacokinetic analysis. The final model, a 2\u2010compartment disposition model with sequential zero\u2010 and first\u2010order absorption, was similar to a previously developed adult model, which identified weight, dose, and Asian race as covariates. Simulations performed using the final model suggested the following dose regimen as appropriate for patients aged 2\u201317\u2009years: 40\u2009mg three times a day for pediatric patients with a BSA of 0.33\u20130.65\u2009m\n                    <jats:sup>2<\/jats:sup>\n                    ; BSA\u2010based dosing (92\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    rounded for 40 and 80\u2009mg capsules) for pediatric patients 2 to &lt;\u200912\u2009years, and BSA \u2265\u20090.66\u2009m\n                    <jats:sup>2<\/jats:sup>\n                    ; and weight\u2010based dosing (120\u2009mg BID &lt;\u200950\u2009kg and 160\u2009mg BID \u2265\u200950\u2009kg) for adolescent patients \u2265\u200912\u2009years.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70042","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T07:54:54Z","timestamp":1747122894000},"page":"1848-1856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Population Pharmacokinetics Modeling of Selpercatinib to Support Posology in Pediatric Patients With\n                    <scp>RET<\/scp>\n                    \u2010Altered Metastatic Thyroid Cancer or Solid Tumors"],"prefix":"10.1002","volume":"14","author":[{"given":"Dan","family":"Liu","sequence":"first","affiliation":[{"name":"Global PKPD and Pharmacometrics Eli Lilly and Company  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-0172","authenticated-orcid":false,"given":"Jan\u2010Stefan","family":"van der Walt","sequence":"additional","affiliation":[{"name":"Occams Co\u00f6peratie U.A  the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(22)00541\u20101"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15164146"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.932353"},{"key":"e_1_2_10_5_1","unstructured":"\u201cFDA Approves Selpercatinib for Lung and Thyroid Cancers With RET Gene Mutations or Fusions.\u201d(2020) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010approves\u2010selpercatinib\u2010lung\u2010and\u2010thyroid\u2010cancers\u2010ret\u2010gene\u2010mutations\u2010or\u2010fusions."},{"key":"e_1_2_10_6_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion\u2010Positive Solid Tumors.\u201d(2022) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010approves\u2010selpercatinib\u2010locally\u2010advanced\u2010or\u2010metastatic\u2010ret\u2010fusion\u2010positive\u2010solid\u2010tumors."},{"key":"e_1_2_10_7_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Grants Accelerated Approval to Selpercatinib for Pediatric Patients Two Years and Older With RET\u2010Altered Metastatic Thyroid Cancer or Solid Tumors.\u201d(2024) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010selpercatinib\u2010pediatric\u2010patients\u2010two\u2010years\u2010and\u2010older\u2010ret\u2010altered."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.10009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005653"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00393"},{"key":"e_1_2_10_11_1","first-page":"30","volume-title":"Population Pharmacokinetics of Selpercatinib in Patients With an Advanced Solid Tumor, Including RET Fusion\u2010Positive NSCLC, RET\u2010Mutant MTC, and Other Tumors With Increased RET Activity","author":"Liu D.","year":"2022"},{"key":"e_1_2_10_12_1","unstructured":"Centers for Disease Control and Prevention \u201c1999\u20102004 Dual Energy X\u2010ray Absorptiometry (DXA) Multiple Imputation Data Files.\u201dhttps:\/\/wwwn.cdc.gov\/nchs\/nhanes\/dxa\/dxafaq.aspx. NHANES."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010014\u20100140\u20107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198710223171717"},{"key":"e_1_2_10_15_1","unstructured":"S. L.Beal L. B.Sheiner A. J.Boeckmann et\u00a0al. \u201cNONMEM 7.5 User's Guides.\u201d(1989\u20102020)."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_10_17_1","unstructured":"R Core Team \u201cR: A Language and Environment for Statistical Computing.\u201d(2019) R Foundation for Statistical Computing Vienna Austria https:\/\/www.R\u2010project.org\/."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010011\u20109255\u2010z"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T03:41:44Z","timestamp":1763782904000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/psp4.70042"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70042","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"assertion":[{"value":"2024-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}