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The aim of the study is to identify an acceptable exposure range, both through the development of a population pharmacokinetic model of vigabatrin in children enabling us to calculate patient exposure and through the study of therapeutic response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective study including children with epilepsy followed at Necker\u2010Enfants Malades hospital who had a vigabatrin assay between January 2019 and January 2022. The population pharmacokinetic study was performed on Monolix2021 using a nonlinear mixed\u2010effects modelling approach. Children treated for epileptic spasms were classified into responder and nonresponder groups according to whether the spasms resolved, in order to identify an effective plasma exposure range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 79 patients and analysed 159 samples. The median age was 4.2\u2009years (range 0.3\u201318). A 2\u2010compartment model with allometry and creatinine clearance on clearance best fit our data. Exposure analysis was performed on 61 patients with epileptic spasms. Of the 22 patients who responded (36%), 95% had an AUC<jats:sub>0\u201324<\/jats:sub> between 264 and 549\u2009mg.h.L<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The population pharmacokinetic model allowed us to identify bodyweight and creatinine clearance as the 2 main factors explaining the observed interindividual variability of vigabatrin. An acceptable exposure range was defined in this study. A target concentration intervention approach using this pharmacokinetic model could be used to avoid overexposure in responder patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16072","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T04:28:43Z","timestamp":1714105723000},"page":"1900-1910","source":"Crossref","is-referenced-by-count":1,"title":["Optimization of vigabatrin dosage in children with epileptic spasms: A population pharmacokinetic approach"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3272-4425","authenticated-orcid":false,"given":"Agathe","family":"Molimard","sequence":"first","affiliation":[{"name":"Service de Neurop\u00e9diatrie et Maladies M\u00e9taboliques, H\u00f4pital Necker\u2010Enfants\u2010malades, AP\u2010HP Universit\u00e9 Paris Cit\u00e9  Paris 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