Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions

Detalhes bibliográficos
Autor(a) principal: Marinho, Aline T.
Data de Publicação: 2014
Outros Autores: Rodrigues, Patrícia M., Caixas, Umbelina, Antunes, Alexandra M.M., Branco, Teresa, Harjivan, Shrika G., Marques, M. Matilde, Monteiro, Emília C., Pereira, Sofia A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/163917
Resumo: Funding Information: This work was supported by Fundac¸ão para a Ciência e a Tecnologia (FCT, Portugal), through research grants (PTDC/SAU-TOX/111663/2009, PTDC/ QUI-QUI/113910/2009, SFRH/BD/80690/2011 to S. G. H.) and strategic funding to Centro de Química Estrutural (PEst-OE/QUI/UI0100/2013).
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spelling Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactionsNevirapine metabolismNevirapine toxicitySex differencesSex-dependent pharmacokineticsPharmacologyMicrobiology (medical)Infectious DiseasesPharmacology (medical)SDG 3 - Good Health and Well-beingFunding Information: This work was supported by Fundac¸ão para a Ciência e a Tecnologia (FCT, Portugal), through research grants (PTDC/SAU-TOX/111663/2009, PTDC/ QUI-QUI/113910/2009, SFRH/BD/80690/2011 to S. G. H.) and strategic funding to Centro de Química Estrutural (PEst-OE/QUI/UI0100/2013).Objectives: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. Methods: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. Results: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. Conclusions: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNMarinho, Aline T.Rodrigues, Patrícia M.Caixas, UmbelinaAntunes, Alexandra M.M.Branco, TeresaHarjivan, Shrika G.Marques, M. MatildeMonteiro, Emília C.Pereira, Sofia A.2024-02-22T00:11:53Z2014-022014-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article7application/pdfhttp://hdl.handle.net/10362/163917eng0305-7453PURE: 83893451https://doi.org/10.1093/jac/dkt359info: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:RCAAP2024-03-11T05:49:36Zoai:run.unl.pt:10362/163917Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:59:55.996833Repositório 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 Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
title Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
spellingShingle Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
Marinho, Aline T.
Nevirapine metabolism
Nevirapine toxicity
Sex differences
Sex-dependent pharmacokinetics
Pharmacology
Microbiology (medical)
Infectious Diseases
Pharmacology (medical)
SDG 3 - Good Health and Well-being
title_short Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
title_full Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
title_fullStr Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
title_full_unstemmed Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
title_sort Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions
author Marinho, Aline T.
author_facet Marinho, Aline T.
Rodrigues, Patrícia M.
Caixas, Umbelina
Antunes, Alexandra M.M.
Branco, Teresa
Harjivan, Shrika G.
Marques, M. Matilde
Monteiro, Emília C.
Pereira, Sofia A.
author_role author
author2 Rodrigues, Patrícia M.
Caixas, Umbelina
Antunes, Alexandra M.M.
Branco, Teresa
Harjivan, Shrika G.
Marques, M. Matilde
Monteiro, Emília C.
Pereira, Sofia A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Marinho, Aline T.
Rodrigues, Patrícia M.
Caixas, Umbelina
Antunes, Alexandra M.M.
Branco, Teresa
Harjivan, Shrika G.
Marques, M. Matilde
Monteiro, Emília C.
Pereira, Sofia A.
dc.subject.por.fl_str_mv Nevirapine metabolism
Nevirapine toxicity
Sex differences
Sex-dependent pharmacokinetics
Pharmacology
Microbiology (medical)
Infectious Diseases
Pharmacology (medical)
SDG 3 - Good Health and Well-being
topic Nevirapine metabolism
Nevirapine toxicity
Sex differences
Sex-dependent pharmacokinetics
Pharmacology
Microbiology (medical)
Infectious Diseases
Pharmacology (medical)
SDG 3 - Good Health and Well-being
description Funding Information: This work was supported by Fundac¸ão para a Ciência e a Tecnologia (FCT, Portugal), through research grants (PTDC/SAU-TOX/111663/2009, PTDC/ QUI-QUI/113910/2009, SFRH/BD/80690/2011 to S. G. H.) and strategic funding to Centro de Química Estrutural (PEst-OE/QUI/UI0100/2013).
publishDate 2014
dc.date.none.fl_str_mv 2014-02
2014-02-01T00:00:00Z
2024-02-22T00:11:53Z
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/10362/163917
url http://hdl.handle.net/10362/163917
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0305-7453
PURE: 83893451
https://doi.org/10.1093/jac/dkt359
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7
application/pdf
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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