Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats.
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10314/3944 https://doi.org/doi.org/10.1016/j.fct.2017.06.015 |
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. |
id |
RCAP_66462b54e4964d4fb809ecbfa238a2d2 |
---|---|
oai_identifier_str |
oai:bdigital.ipg.pt:10314/3944 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats.(-)-Epigallocatechin gallate Licarbazepine Oxcarbazepine P-glycoprotein Pharmacokinetics SilymarinConsidering 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.Food and Chemical Toxicology2018-03-23T22:16:42Z2018-03-232017-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10314/3944https://doi.org/doi.org/10.1016/j.fct.2017.06.015http://hdl.handle.net/10314/3944porFerreira, AnaRodrigues, MárcioMarques, AlexandreFalcão, AmílcarAlves, Gilbertoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-14T02:57:41Zoai:bdigital.ipg.pt:10314/3944Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:43:07.394187Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
title |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
spellingShingle |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. Ferreira, Ana (-)-Epigallocatechin gallate Licarbazepine Oxcarbazepine P-glycoprotein Pharmacokinetics Silymarin |
title_short |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
title_full |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
title_fullStr |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
title_full_unstemmed |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
title_sort |
Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats. |
author |
Ferreira, Ana |
author_facet |
Ferreira, Ana Rodrigues, Márcio Marques, Alexandre Falcão, Amílcar Alves, Gilberto |
author_role |
author |
author2 |
Rodrigues, Márcio Marques, Alexandre Falcão, Amílcar Alves, Gilberto |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Ferreira, Ana Rodrigues, Márcio Marques, Alexandre Falcão, Amílcar Alves, Gilberto |
dc.subject.por.fl_str_mv |
(-)-Epigallocatechin gallate Licarbazepine Oxcarbazepine P-glycoprotein Pharmacokinetics Silymarin |
topic |
(-)-Epigallocatechin gallate Licarbazepine Oxcarbazepine P-glycoprotein Pharmacokinetics Silymarin |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08-01T00:00:00Z 2018-03-23T22:16:42Z 2018-03-23 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10314/3944 https://doi.org/doi.org/10.1016/j.fct.2017.06.015 http://hdl.handle.net/10314/3944 |
url |
http://hdl.handle.net/10314/3944 https://doi.org/doi.org/10.1016/j.fct.2017.06.015 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Food and Chemical Toxicology |
publisher.none.fl_str_mv |
Food and Chemical Toxicology |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799136924216066048 |