Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes
Autor(a) principal: | |
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Data de Publicação: | 2000 |
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/10316/5807 https://doi.org/10.1016/S0378-5173(00)00445-2 |
Resumo: | The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with [beta]-cyclodextrin ([beta]-CD) and hydroxypropyl-[beta]-cyclodextrin (HP-[beta]-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n=6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (Cmax) of 18.58±3.27 [mu]g/ml at 8.5 h (Tmax), whereas with inclusion complexes, Cmax increased about two times and appeared at ca. 4 h. AUC0-24 of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVGmax) of TBM (34.1%) was observed at 5.6 h (Tgmax). CVGmax of TBM/[beta]-CD and TBM/HP-[beta]-CD inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively. AAC0-24 of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity. |
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Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexesCyclodextrinsTolbutamideInclusion complexesBioavailabilityHypoglycaemic activityThe purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with [beta]-cyclodextrin ([beta]-CD) and hydroxypropyl-[beta]-cyclodextrin (HP-[beta]-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n=6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (Cmax) of 18.58±3.27 [mu]g/ml at 8.5 h (Tmax), whereas with inclusion complexes, Cmax increased about two times and appeared at ca. 4 h. AUC0-24 of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVGmax) of TBM (34.1%) was observed at 5.6 h (Tgmax). CVGmax of TBM/[beta]-CD and TBM/HP-[beta]-CD inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively. AAC0-24 of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity.http://www.sciencedirect.com/science/article/B6T7W-40T9G9V-P/1/3f0ee31e925f45ea5e88caafa81737fe2000info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5807http://hdl.handle.net/10316/5807https://doi.org/10.1016/S0378-5173(00)00445-2engInternational Journal of Pharmaceutics. 202:1-2 (2000) 165-171Veiga, F.Fernandes, C.Teixeira, F.info: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:RCAAP2021-11-08T11:11:23Zoai:estudogeral.uc.pt:10316/5807Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:18.932285Repositório 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 |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
title |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
spellingShingle |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes Veiga, F. Cyclodextrins Tolbutamide Inclusion complexes Bioavailability Hypoglycaemic activity |
title_short |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
title_full |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
title_fullStr |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
title_full_unstemmed |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
title_sort |
Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes |
author |
Veiga, F. |
author_facet |
Veiga, F. Fernandes, C. Teixeira, F. |
author_role |
author |
author2 |
Fernandes, C. Teixeira, F. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Veiga, F. Fernandes, C. Teixeira, F. |
dc.subject.por.fl_str_mv |
Cyclodextrins Tolbutamide Inclusion complexes Bioavailability Hypoglycaemic activity |
topic |
Cyclodextrins Tolbutamide Inclusion complexes Bioavailability Hypoglycaemic activity |
description |
The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with [beta]-cyclodextrin ([beta]-CD) and hydroxypropyl-[beta]-cyclodextrin (HP-[beta]-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n=6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (Cmax) of 18.58±3.27 [mu]g/ml at 8.5 h (Tmax), whereas with inclusion complexes, Cmax increased about two times and appeared at ca. 4 h. AUC0-24 of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVGmax) of TBM (34.1%) was observed at 5.6 h (Tgmax). CVGmax of TBM/[beta]-CD and TBM/HP-[beta]-CD inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively. AAC0-24 of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity. |
publishDate |
2000 |
dc.date.none.fl_str_mv |
2000 |
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/10316/5807 http://hdl.handle.net/10316/5807 https://doi.org/10.1016/S0378-5173(00)00445-2 |
url |
http://hdl.handle.net/10316/5807 https://doi.org/10.1016/S0378-5173(00)00445-2 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Pharmaceutics. 202:1-2 (2000) 165-171 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
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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 |
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