Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente

Detalhes bibliográficos
Autor(a) principal: Barroso, Elizabeth Clara
Data de Publicação: 2009
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
dARK ID: ark:/83112/0013000007ps8
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/856
Resumo: Reduced antituberculosis drugs concentrations are associated with Mycobacterium tuberculosis resistance. This study aims to evaluate intestinal permeability and serum concentrations of rifampin (RIF) and isoniazid (INH) in patients with multidrug-resistant tuberculosis (MDR-TB). A case-control was conducted with outpatients who attended Messejana’s Hospital in Fortaleza-Ceará from August 2006 to April 2007. MDR-TB (case) was defined as resistance to at least RIF+INH according to the susceptibility test by the proportion method. Two control groups were formed. The drug sensible TB (DS-TB) group defined so when the isolate was sensible to RIF, INHH, streptomycin and ethambutol and the healthy control group (HC). The final MDR-TB, DS-TB and health control groups composition was 41, 33 and 41 respectively, matched by sex and age. Biochemical and haematological examinatios, lactulose:mannitol (L/M) test (to access intestinal absorption) were performed as well as social and clinical interview in all volunteers. To access the serum concentrations two blood samples were collect at two and six hours after RIF and INH ingestion in 32 MDR-TB and 28 DS-TB patients and 30 HC. The drug serum concentrations and L/M test in urine were performed by HPLC. After univariate analysis the median/range of the L and M urinary excretion percentage was significantly lower in MDR-TB patients comparing to HC (p<0.05). Adjusting for alcoholism+tabagism association or Body Mass Index (BMI), this difference disappeared for lactulose. After multivariate analysis the mean ± standard (sd) deviation M urinary excretion percentage was lower in MDR-TB than in HC (p=0.0291) group or DS-TB (p=0.0369) group. The L:M ratio did not differ between the groups (p=0.4747). The mean±sd of the INH maximum serum concentration (HCmax) was higher in MDR-TB (3.82±1.18) than in HC (2.79±1.19) group, p<0.01 and there was no difference between DS-TB and HC nor between MDR-TB and DS-TB groups. After multivariate analysis the HCmax increased in HC (3.07±0.24), but, remained to be higher in MDR-TB group, and now, significantly higher only than DS-TB group. There was HCmax < 3 µg/ml in 18.8% (6/32) of the cases and 56.7% (17/30) of the HC (p<0.05) and no difference between DS-TB (39.3%, 11/28) and HC. After multivariate analysis the mean±sd RIF maximum serum concentration (RCmax) was lower in MDR-TB than in HC(p,0.05) and in DS-TB than in HC (p<0.001), with no difference between MDR-TB and DS-TB groups. The RCmax was < 8 µg/ml in 90.6% (29/32) of the cases and 66.7% (20/30) of HC (p<0.05) and in 82.1% (23/28) of the DS-TB patients (comparing to HC, p<0.05). In conclusion there was reduction in transcellular intestinal absorption in MDR-TB versus DS-TB or HC and the data suggest that alcoholism+tabagism association and BMI have an important role in the reduction of paracellular transport in MDR-TB patients. The RCmax was low in MDR-TB and DS-TB patients with high proportions of subtherapeutic levels in theses groups, mainly for RCmax, but also worrying for HCmax.
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spelling Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistenteIntestinal barrier function and bioavailability of rifampin and isoniazid in multidrug-resistant tuberculosis patients in ceará state, northeast-braziTuberculose multirresistenteAbsorção IntestinalTuberculoseReduced antituberculosis drugs concentrations are associated with Mycobacterium tuberculosis resistance. This study aims to evaluate intestinal permeability and serum concentrations of rifampin (RIF) and isoniazid (INH) in patients with multidrug-resistant tuberculosis (MDR-TB). A case-control was conducted with outpatients who attended Messejana’s Hospital in Fortaleza-Ceará from August 2006 to April 2007. MDR-TB (case) was defined as resistance to at least RIF+INH according to the susceptibility test by the proportion method. Two control groups were formed. The drug sensible TB (DS-TB) group defined so when the isolate was sensible to RIF, INHH, streptomycin and ethambutol and the healthy control group (HC). The final MDR-TB, DS-TB and health control groups composition was 41, 33 and 41 respectively, matched by sex and age. Biochemical and haematological examinatios, lactulose:mannitol (L/M) test (to access intestinal absorption) were performed as well as social and clinical interview in all volunteers. To access the serum concentrations two blood samples were collect at two and six hours after RIF and INH ingestion in 32 MDR-TB and 28 DS-TB patients and 30 HC. The drug serum concentrations and L/M test in urine were performed by HPLC. After univariate analysis the median/range of the L and M urinary excretion percentage was significantly lower in MDR-TB patients comparing to HC (p<0.05). Adjusting for alcoholism+tabagism association or Body Mass Index (BMI), this difference disappeared for lactulose. After multivariate analysis the mean ± standard (sd) deviation M urinary excretion percentage was lower in MDR-TB than in HC (p=0.0291) group or DS-TB (p=0.0369) group. The L:M ratio did not differ between the groups (p=0.4747). The mean±sd of the INH maximum serum concentration (HCmax) was higher in MDR-TB (3.82±1.18) than in HC (2.79±1.19) group, p<0.01 and there was no difference between DS-TB and HC nor between MDR-TB and DS-TB groups. After multivariate analysis the HCmax increased in HC (3.07±0.24), but, remained to be higher in MDR-TB group, and now, significantly higher only than DS-TB group. There was HCmax < 3 µg/ml in 18.8% (6/32) of the cases and 56.7% (17/30) of the HC (p<0.05) and no difference between DS-TB (39.3%, 11/28) and HC. After multivariate analysis the mean±sd RIF maximum serum concentration (RCmax) was lower in MDR-TB than in HC(p,0.05) and in DS-TB than in HC (p<0.001), with no difference between MDR-TB and DS-TB groups. The RCmax was < 8 µg/ml in 90.6% (29/32) of the cases and 66.7% (20/30) of HC (p<0.05) and in 82.1% (23/28) of the DS-TB patients (comparing to HC, p<0.05). In conclusion there was reduction in transcellular intestinal absorption in MDR-TB versus DS-TB or HC and the data suggest that alcoholism+tabagism association and BMI have an important role in the reduction of paracellular transport in MDR-TB patients. The RCmax was low in MDR-TB and DS-TB patients with high proportions of subtherapeutic levels in theses groups, mainly for RCmax, but also worrying for HCmax.Baixos níveis sangüíneos de drogas antituberculose podem ser causa de resistência do Mycobacterium tuberculosis. Este estudo objetivou avaliar a absorção intestinal transcelular e paracelular e verificar possível repercussão nas concentra-ções séricas de de rifampicina (RMP) e isoniazida (INH) em pacientes com tuberculose multirresistente (TBMR). Realizou-se estudo caso-controle no Ambulatório de Tisiologia do Hospital de Messejana, em Fortaleza-Ceará, entre agosto de 2006 e abril de 2007. TBMR foi definida como o caso de portador de bacilo resistente a pelo menos RMP+INH, de acordo com o teste de sensibilidade realizado pelo método das proporções. Foram formados dois grupos para controle, o dos portadores de tuberculose sensível (TBS) e o dos voluntários sãos (VS). Realizaram-se exames hematológicos e bioquímicos, o teste da lactulose / manitol (L/M) (para avaliar a absorção intestinal) e coleta de dados clínicos e sociais de todos os voluntários. Para a avaliação das concentrações séricas foi coletado sangue duas e seis horas após a ingestão observada da RMP+INH. A técnica utilizada para a quantificação da L e M na urina e dosagem sérica de RMP e INH foi a cromatografia líquida de alta pressão. O total de componentes dos grupos com TBMR, TBS e de sadios foi, respectivamente, 41, 33 e 41, emparelhados por gênero e idade. Na análise univariada, encontrou-se mediana / variação do percentual de excreção urinária da L e M menor no grupo com TBMR em relação aos sadios (p<0,05). Ao se corrigir para a associação alcoolismo + tabagismo ou índice de massa corporal (IMC), desapareceu a significância da menor excreção de lactulose nos portadores de TBMR. Após a análise multivariada, a média±desvio-padrão (dv) do percentual de excreção urinária do M foi menor no grupo com TBMR em relação ao grupo de VS (p=0,0291) e em relação ao de TBS (p=0,0369). A relação L/M foi semelhante entre os grupos (p=0,4747). A concentração sérica máxima de INH (CHX) média±desvio-padrão foi maior no grupo com TBMR (3,82±1,18) em relação ao VS (2,79±1,19), p<0,01, não havendo diferença entre TBS e VS nem entre TBMR e TBS. Após a análise multivariada, a CHX aumentou no grupo VS (3,07±0,24), mas continuou a ser maior no grupo com TBMR e, agora, com diferença significante em relação apenas à TBS. Houve CHX < 3 µg/ml em 18,8% (6/32) dos casos e 56,7% (17/30) dos sadios (p<0,05), não havendo diferença entre TBS, 39,3% (11/28) e sadios. Após a análise multivariada, a media±dp da concentração sérica máxima de RMP (CRX) foi menor no grupo com TBMR do que nos sadios (p<0,05) e no grupo com TBS do que nos sadios (p<0,001), não havendo diferença entre TBMR e TBS. Houve (CRX) < 8 µg/ml em 90,6% (29/32) dos portadores de TBMR e 66,7% (20/30) dos sadios (p<0,05) e em 82,1% (23/28) do grupo com TBS (em relação aos sadios, p<0,05). Em conclusão, observou-se redução na absorção transcelular intestinal em pacientes com TBMR versus TBS ou sadios, e os dados sugerem significante participação do alcoolismo+tabagismo e IMC na redução do transporte paracelular em portadores de TBMR. A CRX foi mais baixa em portadores de TBMR e TBS do que em sadios, com altas proporções de níveis subterapêuticos de RMP e INH nos três grupos, principalmente para CRX, mas, também preocupante para CHX.Lima, Aldo Ângelo MoreiraBarroso, Elizabeth Clara2011-10-07T16:25:18Z2011-10-07T16:25:18Z2009info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfBARROSO, Elizabeth Clara. Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente. 2009. 273 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2009.http://www.repositorio.ufc.br/handle/riufc/856ark:/83112/0013000007ps8porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-16T11:09:41Zoai:repositorio.ufc.br:riufc/856Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:33:46.354273Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
Intestinal barrier function and bioavailability of rifampin and isoniazid in multidrug-resistant tuberculosis patients in ceará state, northeast-brazi
title Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
spellingShingle Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
Barroso, Elizabeth Clara
Tuberculose multirresistente
Absorção Intestinal
Tuberculose
title_short Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
title_full Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
title_fullStr Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
title_full_unstemmed Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
title_sort Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente
author Barroso, Elizabeth Clara
author_facet Barroso, Elizabeth Clara
author_role author
dc.contributor.none.fl_str_mv Lima, Aldo Ângelo Moreira
dc.contributor.author.fl_str_mv Barroso, Elizabeth Clara
dc.subject.por.fl_str_mv Tuberculose multirresistente
Absorção Intestinal
Tuberculose
topic Tuberculose multirresistente
Absorção Intestinal
Tuberculose
description Reduced antituberculosis drugs concentrations are associated with Mycobacterium tuberculosis resistance. This study aims to evaluate intestinal permeability and serum concentrations of rifampin (RIF) and isoniazid (INH) in patients with multidrug-resistant tuberculosis (MDR-TB). A case-control was conducted with outpatients who attended Messejana’s Hospital in Fortaleza-Ceará from August 2006 to April 2007. MDR-TB (case) was defined as resistance to at least RIF+INH according to the susceptibility test by the proportion method. Two control groups were formed. The drug sensible TB (DS-TB) group defined so when the isolate was sensible to RIF, INHH, streptomycin and ethambutol and the healthy control group (HC). The final MDR-TB, DS-TB and health control groups composition was 41, 33 and 41 respectively, matched by sex and age. Biochemical and haematological examinatios, lactulose:mannitol (L/M) test (to access intestinal absorption) were performed as well as social and clinical interview in all volunteers. To access the serum concentrations two blood samples were collect at two and six hours after RIF and INH ingestion in 32 MDR-TB and 28 DS-TB patients and 30 HC. The drug serum concentrations and L/M test in urine were performed by HPLC. After univariate analysis the median/range of the L and M urinary excretion percentage was significantly lower in MDR-TB patients comparing to HC (p<0.05). Adjusting for alcoholism+tabagism association or Body Mass Index (BMI), this difference disappeared for lactulose. After multivariate analysis the mean ± standard (sd) deviation M urinary excretion percentage was lower in MDR-TB than in HC (p=0.0291) group or DS-TB (p=0.0369) group. The L:M ratio did not differ between the groups (p=0.4747). The mean±sd of the INH maximum serum concentration (HCmax) was higher in MDR-TB (3.82±1.18) than in HC (2.79±1.19) group, p<0.01 and there was no difference between DS-TB and HC nor between MDR-TB and DS-TB groups. After multivariate analysis the HCmax increased in HC (3.07±0.24), but, remained to be higher in MDR-TB group, and now, significantly higher only than DS-TB group. There was HCmax < 3 µg/ml in 18.8% (6/32) of the cases and 56.7% (17/30) of the HC (p<0.05) and no difference between DS-TB (39.3%, 11/28) and HC. After multivariate analysis the mean±sd RIF maximum serum concentration (RCmax) was lower in MDR-TB than in HC(p,0.05) and in DS-TB than in HC (p<0.001), with no difference between MDR-TB and DS-TB groups. The RCmax was < 8 µg/ml in 90.6% (29/32) of the cases and 66.7% (20/30) of HC (p<0.05) and in 82.1% (23/28) of the DS-TB patients (comparing to HC, p<0.05). In conclusion there was reduction in transcellular intestinal absorption in MDR-TB versus DS-TB or HC and the data suggest that alcoholism+tabagism association and BMI have an important role in the reduction of paracellular transport in MDR-TB patients. The RCmax was low in MDR-TB and DS-TB patients with high proportions of subtherapeutic levels in theses groups, mainly for RCmax, but also worrying for HCmax.
publishDate 2009
dc.date.none.fl_str_mv 2009
2011-10-07T16:25:18Z
2011-10-07T16:25:18Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv BARROSO, Elizabeth Clara. Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente. 2009. 273 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2009.
http://www.repositorio.ufc.br/handle/riufc/856
dc.identifier.dark.fl_str_mv ark:/83112/0013000007ps8
identifier_str_mv BARROSO, Elizabeth Clara. Estudo da barreira funcional intestinal e concentrações séricas de rifampicina e isoniazida em pacientes com tuberculose multirresistente. 2009. 273 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2009.
ark:/83112/0013000007ps8
url http://www.repositorio.ufc.br/handle/riufc/856
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