{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:45:05Z","timestamp":1791945905584,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The purposes of this study were to explore the pharmacokinetics of perampanel (PER) in children with epilepsy, identify factors that contribute to pharmacokinetic variations among subjects, evaluate the connection between PER exposure and clinical outcome, and establish an evidence\u2010based approach for tailoring individualized antiepileptic treatment in this specific population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective study, PER plasma concentrations and genetic information on metabolic enzymes were obtained from 194 patients younger than 18\u2009years. The disposition kinetics of PER in pediatric patients following oral dosing were characterized using nonlinear mixed effect models. The effective range for the plasma concentration of PER was determined by assessing the efficacy and safety of PER treatment and analyzing the relationship between drug exposure and clinical response. Monte Carlo simulations were then performed to evaluate and optimize the current dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The pharmacokinetic profile of PER was adequately described by a one\u2010compartment model with first\u2010order absorption and elimination. Body weight, total bilirubin level, and concomitant oxcarbazepine were found to have significant influences on PER pharmacokinetics. Model estimates of apparent clearance and volume of distribution were .016\u2009\u00b1\u2009.009\u2009L\/h\/kg and 1.47\u2009\u00b1\u2009.78\u2009L\/kg, respectively. The effective range predicted from plasma concentration data in responders was 215\u2013862\u2009\u03bcg\/L. Dosing scenarios stratified according to essential covariates were proposed through simulation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In this study, we captured the pharmacokinetic\/pharmacodynamic characteristics of PER in pediatric epilepsy patients through analysis of real\u2010world data and adopted a pharmacometric approach to support an individualized dosing strategy for PER in this specific population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17954","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T05:35:14Z","timestamp":1712208914000},"page":"1687-1697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population pharmacokinetics and dosing optimization of perampanel in children with epilepsy: A real\u2010world study"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-1634","authenticated-orcid":false,"given":"Sichan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7214-8739","authenticated-orcid":false,"given":"Jiaqin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Clinical Research Center of Neurodevelopmental Disabilities in Children in Hubei Province  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaLi","family":"Tuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Institution, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Clinical Research Center of Neurodevelopmental Disabilities in Children in Hubei Province  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhisheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Clinical Research Center of Neurodevelopmental Disabilities in Children in Hubei Province  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003509"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03109.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12398"},{"issue":"11","key":"e_1_2_10_5_1","first-page":"683","article-title":"Perampanel (Fycompa): a review of clinical efficacy and safety in epilepsy","volume":"41","author":"Greenwood J","year":"2016","journal-title":"Pharm Ther"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2019.1560420"},{"key":"e_1_2_10_7_1","unstructured":"FDA USFaDA.Clinical pharmacology review.2012. Application number: 202834Orig1s000 [December 27 2023]. Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2012\/202834Orig1s000PharmR.pdf"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1701"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12865"},{"key":"e_1_2_10_10_1","unstructured":"Fycompa\u00ae (perampanel): highlights of prescribing information [Internet].2012[cited Mar 10 2023]. 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