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Biblioteca Digital do IPG >
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Artigos em Revista Internacional (ESS) >
Utilize este identificador para referenciar este registo:
http://hdl.handle.net/10314/3944
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| Título: | Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
| Autores: | Ferreira, Ana
Rodrigues, Márcio
Marques, Alexandre
Falcão, Amílcar
Alves, Gilberto |
| Palavras Chave: | (-)-Epigallocatechin gallate Licarbazepine Oxcarbazepine P-glycoprotein Pharmacokinetics Silymarin |
| Data: | 1-Aug-2017 |
| Editora: | Food and Chemical Toxicology |
| Resumo: | Considering the potential of flavonoids in reversing the P-glycoprotein (P-gp)emediated multidrug resistance, this work aimed to assess the combined effects of silymarin and (-)-epigallocatechin gallate (EPG) on the pharmacokinetics of the P-gp substrates oxcarbazepine (OXC) and licarbazepine (LIC). Rats were pre-treated intraperitoneally with silymarin (25 mg/kg), EPG (25 mg/kg), silymarin/EPG (12.5/
12.5 mg/kg; 6.25/18.75 mg/kg; 18.75/6.25 mg/kg) or verapamil (25 mg/kg, reference P-gp inhibitor)
before the intraperitoneal administration of OXC (50 mg/kg). Pre-treatment with dual silymarin/EPG
combinations originated peak plasma concentrations of OXC and LIC (pharmacologically active metabolite
of OXC) similar to those achieved in the presence of verapamil (positive control). Moreover, the
effects promoted by silymarin/EPG combinations on the magnitude of systemic drug exposure to OXC
and LIC were also reflected in the corresponding drug levels attained in the brain (biophase). These
findings evidence the synergistic effect of silymarin and EPG in enhancing the degree of systemic exposure to OXC and LIC in rats, which occurred in a comparable extent to that observed with verapamil.
Hence, our findings support the combination of flavonoid-type P-gp inhibitors and P-gp substrate
antiepileptic drugs as a potential therapeutic strategy for the management of pharmacoresistant
epilepsy. |
| URI: | http://hdl.handle.net/10314/3944 |
| ISSN: | doi.org/10.1016/j.fct.2017.06.015 |
| Aparece nas Colecções: | Artigos em Revista Internacional (ESS)
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