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This study aimed at investigating whether measurable and clinically relevant concentrations of temozolomide are reached and maintained in CSF for continuous oral administration in pediatric patients. A population pharmacokinetic model was developed to quantify CSF penetration of temozolomide.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eleven pediatric CNS tumor patients (aged 4\u201314\u00a0years) treated with oral temozolomide using a metronomic schedule (24\u201377\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day) were included. Temozolomide concentrations in 28 plasma samples and 64 CSF samples were analyzed by high-performance liquid chromatography. Population pharmacokinetic modeling and simulations were performed using non-linear mixed effects modeling (NONMEM 7.4.2).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Median temozolomide concentrations in plasma and CSF were 0.96 (range 0.24\u20135.99) \u00b5g\/ml and 0.37 (0.06\u20131.76) \u00b5g\/ml, respectively. A two-compartment model (central\/plasma [1], CSF [2]) with first-order absorption, first-order elimination, and a transit compartment between CSF and plasma adequately described the data. Population mean estimates for clearance (CL) and the volume of distribution in the central compartment (V<jats:sub>c<\/jats:sub>) were 3.29 L\/h (95% confidence interval (CI) 2.58\u20133.95) and 10.5 L (8.17\u201314.32), respectively. Based on simulations, we found a median area under the concentration vs. time curve ratio (AUC<jats:sub>CSF<\/jats:sub> \/ AUC<jats:sub>plasma<\/jats:sub> ratio) of 37%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Metronomic oral temozolomide penetrates into the CSF in pediatric patients, with even higher concentration levels compared to adults.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-022-04424-4","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T18:04:23Z","timestamp":1648663463000},"page":"617-627","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics of metronomic temozolomide in cerebrospinal fluid of children with malignant central nervous system tumors"],"prefix":"10.1007","volume":"89","author":[{"given":"S\u00f6ren","family":"B\u00fcsker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"J\u00e4ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Poschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mayr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Al Jalali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedeo A.","family":"Azizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Bilal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lobna","family":"El Tabei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Fuhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-8231","authenticated-orcid":false,"given":"Andreas","family":"Peyrl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"4424_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noaa200","volume":"22","author":"QT Ostrom","year":"2020","unstructured":"Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2020) CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2013\u20132017. 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