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: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10314/3720 |
Resumo: | Considering the potential of flavonoids in reversing the P-glycoprotein (P-gp)–mediated 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_9def299aa615dee94eb664593e08b51e |
---|---|
oai_identifier_str |
oai:bdigital.ipg.pt:10314/3720 |
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 gallateLicarbazepineOxcarbazepineP-glycoproteinPharmacokineticsSilymarinConsidering the potential of flavonoids in reversing the P-glycoprotein (P-gp)–mediated 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.The authors are grateful to FCT - Foundation for Science and Technology (Lisbon, Portugal) for the PhD fellowship of Ana Ferreira (SFRH/BD/84936/2012). This work was also supported by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by FCT (Project UID/Multi/00709/2013).2017-06-19T13:17:13Z2017-06-192017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10314/3720http://hdl.handle.net/10314/3720engFerreira, 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:RCAAP2024-01-14T02:57:21Zoai:bdigital.ipg.pt:10314/3720Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:42:55.497532Repositório 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)–mediated 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 |
2017-06-19T13:17:13Z 2017-06-19 2017-01-01T00:00:00Z |
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/10314/3720 http://hdl.handle.net/10314/3720 |
url |
http://hdl.handle.net/10314/3720 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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_ |
1799136922219577344 |