Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies

Autores
Brstilo, Lucas Joel; Reyes Valenzuela, Gabriela; Caraballo, Roberto Horacio; Pérez Montilla, Carlos Alberto; García Bournissen, Facundo; Caceres Guido, Paulo Arturo; Schaiquevich, Paula Susana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5–366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (β = 0.74 ± 0.1649, p < 0.001), 56.8% with food (β = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (β = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.
Fil: Brstilo, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Pérez Montilla, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: García Bournissen, Facundo. University of Western Ontario; Canadá
Fil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Schaiquevich, Paula Susana. Comisión Nacional de Investigación Científica y Tecnológica; Chile. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Materia
CANNABIDIOL
DRUG-RESISTANT DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES
FOOD EFFECT
KETOGENIC DIET
LEVOTHYROXINE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/221769
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/221769
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic EncephalopathiesBrstilo, Lucas JoelReyes Valenzuela, GabrielaCaraballo, Roberto HoracioPérez Montilla, Carlos AlbertoGarcía Bournissen, FacundoCaceres Guido, Paulo ArturoSchaiquevich, Paula SusanaCANNABIDIOLDRUG-RESISTANT DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIESFOOD EFFECTKETOGENIC DIETLEVOTHYROXINEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5–366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (β = 0.74 ± 0.1649, p < 0.001), 56.8% with food (β = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (β = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.Fil: Brstilo, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Pérez Montilla, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: García Bournissen, Facundo. University of Western Ontario; CanadáFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Comisión Nacional de Investigación Científica y Tecnológica; Chile. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaMultidisciplinary Digital Publishing Institute2023-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/221769Brstilo, Lucas Joel; Reyes Valenzuela, Gabriela; Caraballo, Roberto Horacio; Pérez Montilla, Carlos Alberto; García Bournissen, Facundo; et al.; Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 8; 8-2023; 1-131999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/8/2120info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15082120info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:18:12Zoai:ri.conicet.gov.ar:11336/221769instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:18:12.869CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
title Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
spellingShingle Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
Brstilo, Lucas Joel
CANNABIDIOL
DRUG-RESISTANT DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES
FOOD EFFECT
KETOGENIC DIET
LEVOTHYROXINE
title_short Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
title_full Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
title_fullStr Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
title_full_unstemmed Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
title_sort Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies
dc.creator.none.fl_str_mv Brstilo, Lucas Joel
Reyes Valenzuela, Gabriela
Caraballo, Roberto Horacio
Pérez Montilla, Carlos Alberto
García Bournissen, Facundo
Caceres Guido, Paulo Arturo
Schaiquevich, Paula Susana
author Brstilo, Lucas Joel
author_facet Brstilo, Lucas Joel
Reyes Valenzuela, Gabriela
Caraballo, Roberto Horacio
Pérez Montilla, Carlos Alberto
García Bournissen, Facundo
Caceres Guido, Paulo Arturo
Schaiquevich, Paula Susana
author_role author
author2 Reyes Valenzuela, Gabriela
Caraballo, Roberto Horacio
Pérez Montilla, Carlos Alberto
García Bournissen, Facundo
Caceres Guido, Paulo Arturo
Schaiquevich, Paula Susana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CANNABIDIOL
DRUG-RESISTANT DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES
FOOD EFFECT
KETOGENIC DIET
LEVOTHYROXINE
topic CANNABIDIOL
DRUG-RESISTANT DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES
FOOD EFFECT
KETOGENIC DIET
LEVOTHYROXINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5–366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (β = 0.74 ± 0.1649, p < 0.001), 56.8% with food (β = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (β = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.
Fil: Brstilo, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Pérez Montilla, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: García Bournissen, Facundo. University of Western Ontario; Canadá
Fil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Schaiquevich, Paula Susana. Comisión Nacional de Investigación Científica y Tecnológica; Chile. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
description The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5–366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (β = 0.74 ± 0.1649, p < 0.001), 56.8% with food (β = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (β = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.
publishDate 2023
dc.date.none.fl_str_mv 2023-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/221769
Brstilo, Lucas Joel; Reyes Valenzuela, Gabriela; Caraballo, Roberto Horacio; Pérez Montilla, Carlos Alberto; García Bournissen, Facundo; et al.; Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 8; 8-2023; 1-13
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/221769
identifier_str_mv Brstilo, Lucas Joel; Reyes Valenzuela, Gabriela; Caraballo, Roberto Horacio; Pérez Montilla, Carlos Alberto; García Bournissen, Facundo; et al.; Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 8; 8-2023; 1-13
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/8/2120
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15082120
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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