Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients

Detalhes bibliográficos
Autor(a) principal: Lanchote, Vera Lucia
Data de Publicação: 2015
Outros Autores: Almeida, Roque Pacheco de, Barral, Aldina Maria Prado, Barral Netto, Manoel, Marques, Maria Paula, Moraes, Natália Valadares de, Silva, Angela Maraia da, Souza, Tania M. V, Kurtz, Guilherme Suarez
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/13709
Resumo: Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, Brasil
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spelling Lanchote, Vera LuciaAlmeida, Roque Pacheco deBarral, Aldina Maria PradoBarral Netto, ManoelMarques, Maria PaulaMoraes, Natália Valadares deSilva, Angela Maraia daSouza, Tania M. VKurtz, Guilherme Suarez2016-04-12T13:12:51Z2016-04-12T13:12:51Z2015LANCHOTE, V. L. et al. Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients. British Journal of Clinical Pharmacology, v. 80, n. 5, p. 1160-1168, 2015.1365-2125https://www.arca.fiocruz.br/handle/icict/1370910.1111/bcp.12677engBritish Pharmacological SocietyLeishmanioseLeishmaniose visceralQuimioterapiaInflamaçãoAdultosCitocromo-P450Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFaculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFaculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilFaculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilInstituto Nacional de Câncer. Divisão de Farmacologia. Rio de Janeiro, RJ, BrasilAIMS: The aim of the present study was to investigate the impact of human visceral leishmaniasis (VL) and curative chemotherapy on the activity of cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 in patients from an endemic region in Brazil. METHODS: Adult patients with parasitologically confirmed VL were given a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan, immediately before (Study phase 1), 2-3 days (phase 2) and 3-6 months (phase 3) after curative VL chemotherapy. CYP activity was assessed by the apparent clearance of midazolam (CYP3A), omeprazole/5-hydroxyomeprazol ratio in plasma (CYP2C19) and losartan/E3174 ratio in urine (CYP2C9). RESULTS: Mean values (95% confidence interval) in phases 1, 2 and 3 were, respectively: log apparent midazolam clearance, 1.21 (1.10-1.31), 1.45 (1.32-1.57) and 1.35 (1.26-1.44) ml min(-1) kg(-1) ; omeprazole/5-hydroxyomeprazole ratio, 0.78 (0.61-0.94), 0.45 (0.27-0.63) and 0.37 (0.20-0.55); losartan/E3174 ratio, 0.66 (0.39-0.92), 0.35 (0.20-0.50) and 0.35 (0.16-0.53). Analysis of variance revealed significant differences in CYP3A (P = 0.018) and CYP2C19 (P = 0.008), but not CYP2C9 (P = 0.11) phenotypic activity, across the three study phases. CONCLUSION: The phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during acute VL compared with post-chemotherapy. We propose that increased plasma concentrations of proinflammatory cytokines during active disease account for the suppression of CYP activity. The failure to detect significant changes in CYP2C9 activity in the overall cohort may reflect differential effects of the inflammatory process on the expression of CYP isoforms, although the possibility of insufficient statistical power cannot be dismissed.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/13709/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALLanchote, VL. Impact of visceral....pdfLanchote, VL. Impact of visceral....pdfapplication/pdf1105142https://www.arca.fiocruz.br/bitstream/icict/13709/2/Lanchote%2c%20VL.%20Impact%20of%20visceral....pdfbbbaf0c963858cd545018a3daf83495dMD52TEXTLanchote, VL. Impact of visceral....pdf.txtLanchote, VL. 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dc.title.pt_BR.fl_str_mv Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
title Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
spellingShingle Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
Lanchote, Vera Lucia
Leishmaniose
Leishmaniose visceral
Quimioterapia
Inflamação
Adultos
Citocromo-P450
title_short Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
title_full Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
title_fullStr Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
title_full_unstemmed Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
title_sort Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
author Lanchote, Vera Lucia
author_facet Lanchote, Vera Lucia
Almeida, Roque Pacheco de
Barral, Aldina Maria Prado
Barral Netto, Manoel
Marques, Maria Paula
Moraes, Natália Valadares de
Silva, Angela Maraia da
Souza, Tania M. V
Kurtz, Guilherme Suarez
author_role author
author2 Almeida, Roque Pacheco de
Barral, Aldina Maria Prado
Barral Netto, Manoel
Marques, Maria Paula
Moraes, Natália Valadares de
Silva, Angela Maraia da
Souza, Tania M. V
Kurtz, Guilherme Suarez
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Lanchote, Vera Lucia
Almeida, Roque Pacheco de
Barral, Aldina Maria Prado
Barral Netto, Manoel
Marques, Maria Paula
Moraes, Natália Valadares de
Silva, Angela Maraia da
Souza, Tania M. V
Kurtz, Guilherme Suarez
dc.subject.other.pt_BR.fl_str_mv Leishmaniose
Leishmaniose visceral
Quimioterapia
Inflamação
Adultos
Citocromo-P450
topic Leishmaniose
Leishmaniose visceral
Quimioterapia
Inflamação
Adultos
Citocromo-P450
description Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, Brasil
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-04-12T13:12:51Z
dc.date.available.fl_str_mv 2016-04-12T13:12:51Z
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.citation.fl_str_mv LANCHOTE, V. L. et al. Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients. British Journal of Clinical Pharmacology, v. 80, n. 5, p. 1160-1168, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/13709
dc.identifier.issn.none.fl_str_mv 1365-2125
dc.identifier.doi.none.fl_str_mv 10.1111/bcp.12677
identifier_str_mv LANCHOTE, V. L. et al. Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients. British Journal of Clinical Pharmacology, v. 80, n. 5, p. 1160-1168, 2015.
1365-2125
10.1111/bcp.12677
url https://www.arca.fiocruz.br/handle/icict/13709
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.publisher.none.fl_str_mv British Pharmacological Society
publisher.none.fl_str_mv British Pharmacological Society
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/13709/1/license.txt
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https://www.arca.fiocruz.br/bitstream/icict/13709/3/Lanchote%2c%20VL.%20Impact%20of%20visceral....pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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