Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Patrícia Marques
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/11103
Resumo: Dissertação para obtenção do Grau de Mestre em Biotecnologia
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spelling Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistanceNevirapinePre-diabetesInsulin resistanceDrug toxicityAntioxidant defense systemDissertação para obtenção do Grau de Mestre em BiotecnologiaThe increased incidence of type II diabetes has emerged as a major concern in controlled human immunodeficiency virus (HIV)infection. There is a general lack of data to support the best combined antiretroviral therapy (cART) option to treat HIV-patients with pre-diabetes and nevirapine has been described has a glucose-friendly antiretroviral. On the other hand, it is known that diabetes could influence the pharmacokinetics of several drugs. This aspect is particularly relevant for drugs with narrow therapeutic window, which is the case of nevirapine. To understand if nevirapine is a good choice for pre-diabetic HIV-patients, the effect of insulin resistance in NVP pharmacokinetics as well as the effect of nevirapine on insulin resistance, fasting glycemia and mean arterial pressure was evaluated. Moreover, nevirapine effect on thiols content, an endogenous antioxidant defence system, was also evaluated. To achieve the main goal four groups of female Wistar rat were used: a control group, a control group treated with nevirapine, an insulin resistant group and an insulin resistant group treated with nevirapine. An influence of a pre-diabetic status on nevirapine pharmacokinetic was found. Nevirapine and its phase I metabolites presented changes in disposition and the metabolite profile pattern was changed. Moreover, nevirapine, in a pre-diabetic perspective, is associated with a beneficial effect on fasting glycemia, while it has no effect on sensitivity to insulin or in arterial pressure. Furthermore, nevirapine is associated with a lower degradation of total glutathione. Nevirapine might be a good option for HIV-infected patients at higher risk of develop diabetes or in pre-diabetic condition. Moreover, while further studies are necessary to consolidate this issue, nevirapine might be less toxic in pre-diabetes. Although, the decreased bioavailability of nevirapine in pre-diabetes requires special attention, as an adjustment of nevirapine dose might be required in this subpopulation.Portuguese Foundation for Science and Technology - PTDC/QUI-QUI/113910/2009, PTDC/SAU-ORG/111417/2009Faculdade de Ciências e TecnologiaPereira, SofiaConde, SílviaRUNRodrigues, Patrícia Marques2014-01-21T15:40:04Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/11103TID:201755556enginfo: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:RCAAP2024-03-11T03:45:25Zoai:run.unl.pt:10362/11103Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:20:03.296858Repositório 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 Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
title Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
spellingShingle Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
Rodrigues, Patrícia Marques
Nevirapine
Pre-diabetes
Insulin resistance
Drug toxicity
Antioxidant defense system
title_short Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
title_full Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
title_fullStr Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
title_full_unstemmed Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
title_sort Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance
author Rodrigues, Patrícia Marques
author_facet Rodrigues, Patrícia Marques
author_role author
dc.contributor.none.fl_str_mv Pereira, Sofia
Conde, Sílvia
RUN
dc.contributor.author.fl_str_mv Rodrigues, Patrícia Marques
dc.subject.por.fl_str_mv Nevirapine
Pre-diabetes
Insulin resistance
Drug toxicity
Antioxidant defense system
topic Nevirapine
Pre-diabetes
Insulin resistance
Drug toxicity
Antioxidant defense system
description Dissertação para obtenção do Grau de Mestre em Biotecnologia
publishDate 2014
dc.date.none.fl_str_mv 2014-01-21T15:40:04Z
2014
2014-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/11103
TID:201755556
url http://hdl.handle.net/10362/11103
identifier_str_mv TID:201755556
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.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
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
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