{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:48Z","timestamp":1788454848973,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A twice\u2010daily administration of oral selumetinib (SLT) in the fasted state is the only approved pharmaceutical option for treating inoperable neurofibromatosis type I (NF\u20101) and plexiform neurofibromas (PN). In children, exposure to SLT is highly variable, and fasting presents a substantial burden. Therapeutic drug monitoring and pharmacokinetic modeling can support individualized therapy accompanied by a more rational alimentary routine. Twenty\u2010eight children diagnosed with inoperable NF\u20101 or PN were recruited at a major pediatric oncological center. Twenty\u2010two patients donated 156 blood samples in steady state for nonparametric population pharmacokinetic modeling. An equation was developed experimentally for estimating model error. Eleven three\u2010compartment models were compared in terms of statistical performance. Monte Carlo simulations were performed to validate a limited external model using six additional patients and to compare the trough\u2010to\u2010peak SLT concentration ratios simulated for various dosing regimens to develop better control over exposure. A pharmacokinetic model that included total body weight as a covariate provided the best fit between predicted and observed concentrations (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.994) and the best performance statistics. In the first Monte Carlo simulation, measured concentrations fell within the 0.01%\u201395% (median: 19.7%) quantiles of the simulated ranges. The second simulation revealed that 6\u2010h (q6h), 8\u2010h (q8h), and 12\u2010h (q12h) dosing intervals would yield comparable trough\u2010to\u2010peak concentration ratios, with medians of 0.126 (range: 0.001\u20130.335), 0.104 (0.000\u20130.306), and 0.065 (0.000\u20130.279), respectively. The nonparametric population model provides efficient priors for making individual predictions of SLT concentrations. The simulation did not reveal any disadvantages of q6h or q8h dosing.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70156","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T07:43:44Z","timestamp":1764575024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Nonparametric Population Pharmacokinetic Model of Selumetinib in Pediatric Patients Diagnosed With Neurofibromatosis\u2010I or Plexiform Neurofibromas"],"prefix":"10.1002","volume":"15","author":[{"given":"Zolt\u00e1n","family":"K\u00f6ll\u0151","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janka","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"T\u0171zolt\u00f3 Street Department, Pediatric Center Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-8276","authenticated-orcid":false,"given":"Michael N.","family":"Neely","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacokinetics and Bioinformatics, the Saban Research Institute, University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0055-7346","authenticated-orcid":false,"given":"Barna","family":"V\u00e1s\u00e1rhelyi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-3357","authenticated-orcid":false,"given":"Edit","family":"Br\u00fcckner","sequence":"additional","affiliation":[{"name":"T\u0171zolt\u00f3 Street Department, Pediatric Center Semmelweis University  Budapest 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