{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T20:24:31Z","timestamp":1768595071123,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low\u2010 and high\u2010fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N\u2010desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received \u22651 dose of selumetinib and provided \u22651 measurable postdose concentration of selumetinib and N\u2010desmethyl selumetinib. A 2\u2010compartment model with sequential 0\u2010 and 1st\u2010order delayed absorption and 1st\u2010order elimination adequately described selumetinib PK characteristics. A 1\u2010compartment model reasonably described N\u2010desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration\u2013time curve\u00a0ratio (1\u2010sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low\u2010fat meal and 79.3% (76.3%) with a high\u2010fat meal versus fasting. The lower bound of the 1\u2010sided 90% CI demonstrated a difference of &lt;30% between fed and fasted states. Considering the flat exposure\u2010response relationship within the dose range (20\u201030\u00a0mg\/m<jats:sup>2<\/jats:sup>), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant.<\/jats:p>","DOI":"10.1002\/cpdd.1400","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T08:24:39Z","timestamp":1712651079000},"page":"770-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1\u2010Related Plexiform Neurofibromas and Healthy Volunteers"],"prefix":"10.1002","volume":"13","author":[{"given":"Peiying","family":"Zuo","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences Alexion, AstraZeneca Rare Disease  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Million","family":"Arefayene","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences Alexion, AstraZeneca Rare Disease  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Jian","family":"Pan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences Alexion, AstraZeneca Rare Disease  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Freshwater","sequence":"additional","affiliation":[{"name":"Quantitative Pharmacology and Pharmacometrics Immune\/Oncology (QP2\u2010I\/O) Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Monteleone","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences Alexion, AstraZeneca Rare Disease  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70063-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2194"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3345\/cep.2020.00871"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-75"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.5.311"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac146"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912735"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00967-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1150"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605943"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1732-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2017.08.022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3143-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-017-2217-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1295"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1935"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.848"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2153-7"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-021-04274-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.09.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13404"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03339-2"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2022.02.009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13209"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12175"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2016-0082"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12611"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T01:40:05Z","timestamp":1720057205000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,9]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/cpdd.1400"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1400","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,9]]},"assertion":[{"value":"2023-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}