{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:27:06Z","timestamp":1790774826747,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"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":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Identifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug\u2010resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from two pharmacokinetic studies of patients aged 2\u201318\u2009years with DEEs were included (<jats:italic>N<\/jats:italic>\u2009=\u200948 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6\u2009h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD\u2010enriched formulation. Samples were quantified using a validated liquid chromatography\/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed\u2010effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the concentration\u2013time curve between 0 and 12\u2009h (AUC<jats:sub>0\u201012<\/jats:sub>) were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A one\u2010compartment model with transit compartments and first\u2010order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL\/F) and volume of distribution (V\/F) were 143.5\u2009L\/h and 1892.4\u2009L, respectively. Weight was allometrically scaled for V\/F and CL\/F, sex was associated with V\/F, and both formulation and food condition were associated with F (relative bioavailability). CBD C<jats:sub>max<\/jats:sub> increased by 41% and AUC<jats:sub>0\u201012<\/jats:sub> by 45% when CBD was administered with food compared to fasting. Dose\u2010normalized AUC<jats:sub>0\u201012<\/jats:sub> was approximately 50% lower with CBD\u2010enriched oil compared to purified CBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18255","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T14:49:32Z","timestamp":1736779772000},"page":"1143-1154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Population pharmacokinetics of cannabidiol and the impact of food and formulation on systemic exposure in children with drug\u2010resistant developmental and epileptic encephalopathies"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6222-003X","authenticated-orcid":false,"given":"Lucas","family":"Brstilo","sequence":"first","affiliation":[{"name":"Unit of Innovative Treatments Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires Argentina"},{"name":"National Scientific and 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Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3186-8323","authenticated-orcid":false,"given":"Ignacio","family":"Bressan","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry Hospital Italiano de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Marin","sequence":"additional","affiliation":[{"name":"Polyvalent Day Hospital Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Fabiana","family":"Delaven","sequence":"additional","affiliation":[{"name":"Polyvalent Day Hospital Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Agostini","sequence":"additional","affiliation":[{"name":"Polyvalent Day Hospital Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos P\u00e9rez","family":"Montilla","sequence":"additional","affiliation":[{"name":"Parasitology and Chagas Unit, Multidisciplinary Institute for Research on Pediatric Diseases Hospital de Ni\u00f1os \u201cRicardo Gutierrez\u201d  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Emilia","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Food Services Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"Cresta","sequence":"additional","affiliation":[{"name":"Department of Food Services Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires 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