Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10316/101121
Título: | Disposition of eslicarbazepine acetate in the mouse after oral administration | Autor: | Alves, Gilberto Figueiredo, Isabel Castel-Branco, Margarida Lourenço, Nulita Falcão, Amílcar Caramona, Margarida Soares-da-Silva, Patrício |
Palavras-chave: | eslicarbazepine acetate; metabolism; mouse; oxcarbazepine; tissue disposition | Data: | 2008 | Editora: | Société Française de Pharmacologie et de Thérapeutique | Projeto: | info:eu-repo/grantAgreement/FCT/PIDDAC/SFRH/BD/12694/2003/PT/CARACTERIZAÇÃO DO PERFIL NEUROFARMACOCINÉTICO DO BIA 2-093 E DOS SEUS METABOLITOS EM MURGANHOS | Título da revista, periódico, livro ou evento: | Fundamental & Clinical Pharmacology | Volume: | 22 | Número: | 5 | Resumo: | Eslicarbazepine acetate is a promising antiepileptic drug structurally related to carbamazepine and oxcarbazepine, which is in the final phase of clinical development. The metabolism of eslicarbazepine acetate is clearly species dependent and, in this case, among small laboratory animals, the mouse seems to be the most relevant species to humans. Hence, the aim of this study was to investigate the plasma, brain and liver disposition of eslicarbazepine acetate in mice to better understand its disposition in humans. Adult male CD-1 mice were treated orally with a single dose of eslicarbazepine acetate 350 mg/kg. Blood samples, brain and liver tissues were taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 10, 16 and 24 h post-dose. Plasma and tissue levels of eslicarbazepine acetate and its metabolites (S-licarbazepine, R-licarbazepine and oxcarbazepine) were assessed by using high-performance liquid chromatographyultraviolet detection. Both eslicarbazepine acetate and R-licarbazepine concentrations were below the limit of quantification of the assay in all matrices. Eslicarbazepine acetate was rapidly and extensively metabolized to S-licarbazepine (major metabolite), which was oxidized to oxcarbazepine to a small extent. The brain/plasma ratios suggest that the brain exposure to S-licarbazepine and oxcarbazepine was approximately 30% of their total systemic exposure. However, S-licarbazepine crossed the blood–brain barrier (BBB) less efficiently than oxcarbazepine. On the other hand, the liver/plasma ratios support the notion that S-licarbazepine undergoes hepatic accumulation, whereas oxcarbazepine appears to leave this compartment twice as fast as S-licarbazepine. Thus, the diffusion through the BBB is favourable to oxcarbazepine and the liver acts like a deposit of the pharmacologically active metabolite of eslicarbazepine acetate (S-licarbazepine). | URI: | https://hdl.handle.net/10316/101121 | DOI: | 10.1111/j.1472-8206.2008.00617.x | Direitos: | openAccess |
Aparece nas coleções: | FFUC- Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
RIt-11_Disposition_of_eslicarbazepine_acetate_in_the_mouse_after_oral_administration_2008.pdf | 157.05 kB | Adobe PDF | Ver/Abrir |
Citações SCOPUSTM
13
Visto em 17/nov/2022
Citações WEB OF SCIENCETM
13
Visto em 2/mai/2023
Visualizações de página
107
Visto em 2/out/2024
Downloads
100
Visto em 2/out/2024
Google ScholarTM
Verificar
Altmetric
Altmetric
Este registo está protegido por Licença Creative Commons