{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:10:26Z","timestamp":1781867426723,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1007117","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007117","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T17:27:40Z","timestamp":1560446860000},"page":"e1007117","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Development of a physiologically-based pharmacokinetic pediatric brain model for prediction of cerebrospinal fluid drug concentrations and the influence of meningitis"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-898X","authenticated-orcid":true,"given":"Laurens F. M.","family":"Verscheijden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan B.","family":"Koenderink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0502-0647","authenticated-orcid":true,"given":"Saskia N.","family":"de Wildt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-2314","authenticated-orcid":true,"given":"Frans G. M.","family":"Russel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"issue":"3","key":"ref1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1136\/adc.2006.114835","article-title":"The problems in scaling adult drug doses to children","volume":"93","author":"TN Johnson","year":"2008","journal-title":"Arch Dis Child"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1208\/s12248-018-0187-8","article-title":"Pediatric Dose Selection and Utility of PBPK in Determining Dose","volume":"20","author":"IE Templeton","year":"2018","journal-title":"AAPS J"},{"issue":"2","key":"ref3","doi-asserted-by":"crossref","first-page":"e1004495","DOI":"10.1371\/journal.pcbi.1004495","article-title":"Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction","volume":"12","author":"J Lu","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40495-016-0059-9","article-title":"Recent Advances in Development and Application of Physiologically-Based Pharmacokinetic (PBPK) Models: a Transition from Academic Curiosity to Regulatory Acceptance","volume":"2","author":"M. Jamei","year":"2016","journal-title":"Curr Pharmacol Rep"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s10637-010-9585-1","article-title":"The plasma and cerebrospinal fluid pharmacokinetics of sorafenib after intravenous administration in non-human primates","volume":"30","author":"A Kim","year":"2012","journal-title":"Invest New Drugs"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1365-2125.1999.00948.x","article-title":"Morphine and morphine-6-glucuronide in the plasma and cerebrospinal fluid of children","volume":"48","author":"RD Hain","year":"1999","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"ref7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2125.1992.tb04112.x","article-title":"Plasma and Cerebrospinal-Fluid Concentrations of Paracetamol after a Single Intravenous Dose of Propacetamol","volume":"34","author":"B Bannwarth","year":"1992","journal-title":"Brit J Clin Pharmaco"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.dmpk.2016.03.005","article-title":"Development of a permeability-limited model of the human brain and cerebrospinal fluid (CSF) to integrate known physiological and biological knowledge: Estimating time varying CSF drug concentrations and their variability using in vitro data","volume":"31","author":"L Gaohua","year":"2016","journal-title":"Drug Metab Pharmacokinet"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11095-016-2065-3","article-title":"A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations","volume":"34","author":"Y Yamamoto","year":"2017","journal-title":"Pharm Res"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/psp4.12250","article-title":"Predicting Drug Concentration-Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically-Based Pharmacokinetic Model","volume":"6","author":"Y Yamamoto","year":"2017","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejps.2017.11.011","article-title":"Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach","volume":"112","author":"Y Yamamoto","year":"2018","journal-title":"Eur J Pharm Sci"},{"key":"ref12","article-title":"Combining brain microdialysis and translational pharmacokinetic modeling to predict drug concentrations in pediatric severe traumatic brain injury: the next step towards evidence-based pharmacotherapy?","author":"N Ketharanathan","year":"2018","journal-title":"J Neurotrauma"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1128\/CMR.00007-10","article-title":"Penetration of drugs through the blood-cerebrospinal fluid\/blood-brain barrier for treatment of central nervous system infections","volume":"23","author":"R Nau","year":"2010","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"ref14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S1473-3099(09)70306-8","article-title":"Acute bacterial meningitis in infants and children","volume":"10","author":"KS Kim","year":"2010","journal-title":"Lancet Infect Dis"},{"issue":"7","key":"ref15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1533-2500.2012.00556.x","article-title":"Plasma and Cerebrospinal Fluid Pharmacokinetic Parameters After Single-Dose Administration of Intravenous, Oral, or Rectal Acetaminophen","volume":"12","author":"NK Singla","year":"2012","journal-title":"Pain Pract"},{"key":"ref16","article-title":"Neurobiology of Cerebrospinal Fluid 1","author":"JH Wood","year":"1980"},{"issue":"11","key":"ref17","doi-asserted-by":"crossref","first-page":"6619","DOI":"10.1128\/AAC.00997-16","article-title":"Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery","volume":"60","author":"C Lu","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1021\/mp400533q","article-title":"A physiologically based modeling strategy during preclinical CNS drug development","volume":"11","author":"K Ball","year":"2014","journal-title":"Mol Pharm"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1208\/s12248-013-9496-0","article-title":"Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier\u2014towards a mechanistic IVIVE-based approach","volume":"15","author":"K Ball","year":"2013","journal-title":"AAPS J"},{"key":"ref20","article-title":"Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies","author":"E Germovsek","year":"2018","journal-title":"J Antimicrob Chemother"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1093\/infdis\/166.2.350","article-title":"Blood-brain barrier damage in patients with bacterial meningitis: association with tumor necrosis factor-alpha but not interleukin-1 beta","volume":"166","author":"MK Sharief","year":"1992","journal-title":"J Infect Dis"},{"issue":"8","key":"ref22","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1128\/AAC.42.8.2012","article-title":"Disposition and elimination of meropenem in cerebrospinal fluid of hydrocephalic patients with external ventriculostomy","volume":"42","author":"R Nau","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3389\/fimmu.2017.00597","article-title":"Sepsis-Associated Encephalopathy: The Blood-Brain Barrier and the Sphingolipid Rheostat","volume":"8","author":"SJ Kuperberg","year":"2017","journal-title":"Front Immunol"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1471-4159.2011.07208.x","article-title":"Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors","volume":"117","author":"Y Uchida","year":"2011","journal-title":"J Neurochem"},{"issue":"24","key":"ref25","doi-asserted-by":"crossref","first-page":"7454","DOI":"10.1158\/1078-0432.CCR-17-0983","article-title":"Quantitative and Mechanistic Understanding of AZD1775 Penetration across Human Blood-Brain Barrier in Glioblastoma Patients Using an IVIVE-PBPK Modeling Approach","volume":"23","author":"J Li","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"4","key":"ref26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/pr.2015.119","article-title":"The ontogeny of P-glycoprotein in the developing human blood-brain barrier: implication for opioid toxicity in neonates","volume":"78","author":"J Lam","year":"2015","journal-title":"Pediatr Res"},{"issue":"4","key":"ref27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1055\/s-0028-1103272","article-title":"ABC transporter (P-gp\/ABCB1, MRP1\/ABCC1, BCRP\/ABCG2) expression in the developing human CNS","volume":"39","author":"M Daood","year":"2008","journal-title":"Neuropediatrics"},{"issue":"3","key":"ref28","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1542\/peds.2013-4060","article-title":"Off-label use of drugs in children","volume":"133","author":"DA Frattarelli","year":"2014","journal-title":"Pediatrics"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/clpt.2012.64","article-title":"Physiologically based pharmacokinetic (PBPK) modeling in children","volume":"92","author":"JS Barrett","year":"2012","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/clpt.2012.65","article-title":"Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation of ADME: a marriage under the arch of systems pharmacology","volume":"92","author":"A. Rostami-Hodjegan","year":"2012","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"ref31","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/10408440390242324","article-title":"Modeling interindividual variation in physiological factors used in PBPK models of humans","volume":"33","author":"PS Price","year":"2003","journal-title":"Crit Rev Toxicol"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2133\/dmpk.24.53","article-title":"A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: A tale of &apos;bottom-up&apos; vs &apos;top-down&apos; recognition of covariates","volume":"24","author":"M Jamei","year":"2009","journal-title":"Drug Metab Pharmacokinet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2193-9616-1-9","article-title":"The simcyp population based simulator: architecture, implementation, and quality assurance","volume":"1","author":"M Jamei","year":"2013","journal-title":"In Silico Pharmacol"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1517\/17425250802691074","article-title":"The Simcyp population-based ADME simulator","volume":"5","author":"M Jamei","year":"2009","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref35","unstructured":"Simcyp. 17.0.90.0 ed. available from: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.certara.com\/\" xlink:type=\"simple\">https:\/\/www.certara.com\/<\/ext-link>."},{"issue":"6","key":"ref36","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/jps.20322","article-title":"Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases","volume":"94","author":"T Rodgers","year":"2005","journal-title":"J Pharm Sci"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/jps.20502","article-title":"Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions","volume":"95","author":"T Rodgers","year":"2006","journal-title":"J Pharm Sci"},{"issue":"5","key":"ref38","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1007\/s11095-006-9210-3","article-title":"Mechanistic approaches to volume of distribution predictions: understanding the processes","volume":"24","author":"T Rodgers","year":"2007","journal-title":"Pharm Res"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"414","DOI":"10.55782\/ane-2008-1708","article-title":"The choroid plexus\u2014cerebrospinal fluid system: undervaluated pathway of neuroendocrine signaling into the brain","volume":"68","author":"J Skipor","year":"2008","journal-title":"Acta Neurobiol Exp (Wars)"},{"issue":"2","key":"ref40","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/bja\/aew185","article-title":"Cerebrospinal fluid volume in neonates undergoing spinal anaesthesia: a descriptive magnetic resonance imaging study","volume":"117","author":"A Rochette","year":"2016","journal-title":"Br J Anaesth"},{"issue":"5","key":"ref41","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/jnnp.49.5.536","article-title":"Cerebrospinal fluid hydrodynamic studies in children","volume":"49","author":"HK Blomquist","year":"1986","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"ref42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000048344","article-title":"Measurement of cerebrospinal fluid output through external ventricular drainage in one hundred infants and children: correlation with cerebrospinal fluid production","volume":"36","author":"T Yasuda","year":"2002","journal-title":"Pediatr Neurosurg"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/ana.410040410","article-title":"Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights","volume":"4","author":"AS Dekaban","year":"1978","journal-title":"Ann Neurol"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1159\/000456711","article-title":"Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus","volume":"38","author":"NN Andescavage","year":"2016","journal-title":"Dev Neurosci"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1203\/01.PDR.0000130472.30874.FF","article-title":"Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants","volume":"56","author":"P Ballabh","year":"2004","journal-title":"Pediatr Res"},{"key":"ref46","article-title":"Fetal Physiologically Based Pharmacokinetic Models: Systems Information on the Growth and Composition of Fetal Organs","author":"K Abduljalil","year":"2018","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"ref47","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.bbamem.2008.10.022","article-title":"The blood-brain barrier in brain homeostasis and neurological diseases","volume":"1788","author":"N Weiss","year":"2009","journal-title":"Biochim Biophys Acta"},{"issue":"Suppl 2","key":"ref48","doi-asserted-by":"crossref","first-page":"S266","DOI":"10.1093\/clinids\/24.Supplement_2.S266","article-title":"The pharmacology of meropenem, a new carbapenem antibiotic","volume":"24","author":"WA Craig","year":"1997","journal-title":"Clin Infect Dis"},{"issue":"Suppl 1","key":"ref49","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1086\/590064","article-title":"Pharmacokinetic and pharmacodynamic properties of meropenem","volume":"47","author":"DP Nicolau","year":"2008","journal-title":"Clin Infect Dis"},{"issue":"4","key":"ref50","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/bja\/85.4.599","article-title":"The role of albumin in critical illness","volume":"85","author":"JP Nicholson","year":"2000","journal-title":"Br J Anaesth"},{"issue":"7","key":"ref51","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s40262-016-0475-3","article-title":"Development of a Physiologically Based Pharmacokinetic Modelling Approach to Predict the Pharmacokinetics of Vancomycin in Critically Ill Septic Patients","volume":"56","author":"C Radke","year":"2017","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"ref52","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1542\/peds.2006-3378","article-title":"Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration","volume":"119","author":"E Kumpulainen","year":"2007","journal-title":"Pediatrics"},{"issue":"10","key":"ref53","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1177\/0091270011418658","article-title":"Plasma and Cerebrospinal Fluid Pharmacokinetics of Naproxen in Children","volume":"52","author":"P Valitalo","year":"2012","journal-title":"Journal of Clinical Pharmacology"},{"issue":"4","key":"ref54","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-2125.2010.03720.x","article-title":"Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children","volume":"70","author":"E Kumpulainen","year":"2010","journal-title":"Br J Clin Pharmacol"},{"issue":"4","key":"ref55","doi-asserted-by":"crossref","first-page":"E1002","DOI":"10.1542\/peds.2007-0064","article-title":"Cerebrospinal fluid distribution of ibuprofen after intravenous administration in children","volume":"120","author":"H Kokki","year":"2007","journal-title":"Pediatrics"},{"issue":"9","key":"ref56","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/jcph.307","article-title":"Plasma and cerebrospinal fluid concentrations of ibuprofen in pediatric patients and antipyretic effect: Pharmacokinetic-pharmacodynamic modeling analysis","volume":"54","author":"R Har-Even","year":"2014","journal-title":"Journal of Clinical Pharmacology"},{"issue":"Suppl 2","key":"ref57","doi-asserted-by":"crossref","first-page":"S249","DOI":"10.1093\/clinids\/24.Supplement_2.S249","article-title":"Pharmacokinetics of meropenem in animals, healthy volunteers, and patients","volume":"24","author":"YS Moon","year":"1997","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ref58","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5414\/CPP42050","article-title":"Bioequivalence study comparing a new paracetamol solution for injection and propacetamol after single intravenous infusion in healthy subjects","volume":"42","author":"B Flouvat","year":"2004","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"11","key":"ref59","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1124\/dmd.115.065920","article-title":"Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification","volume":"43","author":"JE Sager","year":"2015","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"ref60","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/MJT.0b013e31824ddee3","article-title":"Naive pooled-data approach for pharmacokinetic studies in pediatrics with a very small sample size","volume":"21","author":"I. Mahmood","year":"2014","journal-title":"Am J Ther"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1007117","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T18:25:45Z","timestamp":1721413545000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007117"}},"subtitle":[],"editor":[{"given":"James","family":"Gallo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007117","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1007117","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,13]]}}}