{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:48:10Z","timestamp":1789832890660,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773891"],"award-info":[{"award-number":["81773891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methotrexate (MTX) pharmacokinetics has substantial inter\u2010individual variability and toxicity. In children with medulloblastoma treated with high\u2010dose methotrexate (HD\u2010MTX), the pharmacokinetic properties of methotrexate have not been established. A total of 660 serum samples from 105 pediatric patients with medulloblastoma were included in a population pharmacokinetic (PPK) analysis of methotrexate by using the nonlinear mixed\u2010effects modeling method. The basic one\u2010compartment population pharmacokinetic model was established by NONMEM software and the first\u2010order conditional estimation (FOCE) method, and the final covariate model was obtained by the stepwise regression method. Weight (WT), creatinine clearance (CrCL), and whether the treatment was combined with dexamethasone (DEX) were covariates that had significant effects on the clearance rate (CL) of the model. The pharmacokinetic equation of CL in the final covariate model was as follows: CL<jats:sub>i<\/jats:sub> = 9.23\u00d7 (1 + 0.0005\u00d7 (\u03b8<jats:sub>CrCL<\/jats:sub>\u2010105.78)) \u00d7 (1 + 0.0017\u00d7 (\u03b8<jats:sub>WT<\/jats:sub>\u201016)) \u00d7 e<jats:sup>\u03b7cl,i<\/jats:sup> (L\/h), IF (\u03b8<jats:sub>DEX<\/jats:sub>) CL<jats:sub>i<\/jats:sub> = 1.19\u00d7 CL<jats:sub>i<\/jats:sub> (L\/h). The estimation accuracy of all pharmacokinetic parameters were acceptable (relative standard error &lt; 14.74%). The goodness\u2010of\u2010fit diagram and bootstrap tests indicated that the final PPK model was stable with acceptable predictive ability. The PPK model may be useful for determining personalized medication levels in pediatric medulloblastoma patients undergoing HD\u2010MTX therapy.<\/jats:p>","DOI":"10.1002\/bdd.2221","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T06:09:18Z","timestamp":1580796558000},"page":"101-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Population pharmacokinetics of high\u2010dose methotrexate in Chinese pediatric patients with medulloblastoma"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4394-6237","authenticated-orcid":false,"given":"Zheng\u2010yuan","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Beijing Shijitan Hospital Capital Medical University  Beijing 100038 China"},{"name":"Beijing Key Laboratory of Bio\u2010characteristic Profiling for Evaluation of Clinical Rational Drug Use  Beijing 100038 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