Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes

Detalhes bibliográficos
Autor(a) principal: Veiga, F.
Data de Publicação: 2000
Outros Autores: Fernandes, C., Teixeira, F.
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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spelling 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
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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
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eu_rights_str_mv openAccess
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