{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:04:10Z","timestamp":1791227050934,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Oxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent\u2010metabolite population pharmacokinetic model in children was developed to evaluate the consistency between the recommended paediatric doses and the reference range for trough concentration (C<jats:sub>trough<\/jats:sub>) of MHD (3\u201335\u00a0mg\u00a0l<jats:sup>\u20131<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 279 plasma samples were obtained from 31 epileptic children (age 2\u201312 years) after a single dose of oxcarbazepine. Concentration\u2010time data were analysed with Monolix 4.3.2. The probability to obtain C<jats:sub>trough<\/jats:sub> between 3\u201335\u00a0mg\u00a0l<jats:sup>\u20131<\/jats:sup> was determined by Monte Carlo simulations for doses ranging from 10 to 90\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A parent\u2010metabolite model with two compartments for oxcarbazepine and one compartment for MHD best described the data. Typical values for oxcarbazepine clearance, central and peripheral distribution volume and distribution clearance were 140\u00a0l\u00a0h<jats:sup>\u20131<\/jats:sup>\u00a070\u00a0kg<jats:sup>\u20131<\/jats:sup>, 337\u00a0l\u00a070\u00a0kg<jats:sup>\u20131<\/jats:sup>, 60.7\u00a0l and 62.5\u00a0l\u00a0h<jats:sup>\u20131<\/jats:sup>, respectively. Typical values for MHD clearance and distribution volume were 4.11\u00a0l\u00a0h<jats:sup>\u20131<\/jats:sup>\u00a070\u00a0kg<jats:sup>\u20131<\/jats:sup> and 54.8\u00a0l\u00a070\u00a0kg<jats:sup>\u20131<\/jats:sup> respectively. Clearances and distribution volumes of oxcarbazepine and MHD were related to body weight via empirical allometric models. Enzyme\u2010inducing antiepileptic drugs (EIAEDs) increased MHD clearance by 29.3%. Fifty\u2010kg children without EIAEDs may need 20\u201330\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup> instead of the recommended target maintenance dose (30\u201345\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup>) to obtain C<jats:sub>trough<\/jats:sub> within the reference range. By contrast, 10\u2010kg children with EIAEDs would need 90\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup> instead of the maximum recommended dose of 60\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This population pharmacokinetic model of oxcarbazepine supports current dose recommendations, except for 10\u2010kg children with concomitant EIAEDs and 50\u2010kg children without EIAEDs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13392","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T20:02:42Z","timestamp":1501790562000},"page":"2695-2708","source":"Crossref","is-referenced-by-count":31,"title":["Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-5542","authenticated-orcid":false,"given":"Christelle","family":"Rodrigues","sequence":"first","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Chiron","sequence":"additional","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Rey","sequence":"additional","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Dulac","sequence":"additional","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Comets","sequence":"additional","affiliation":[{"name":"INSERM, IAME, UMR1137 Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"INSERM, CIC 1414 Universit\u00e9 Rennes 1  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Pons","sequence":"additional","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jullien","sequence":"additional","affiliation":[{"name":"INSERM U1129  Paris France"},{"name":"Paris Descartes University, CEA  Gif\u2010sur\u2010Yvette France"},{"name":"Service de Pharmacologie H\u00f4pital Europ\u00e9en Georges Pompidou  20 rue Leblanc 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Full prescribing information. 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