Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis

Detalhes bibliográficos
Autor(a) principal: Rivera, Juan Gonzalo Bardalez
Data de Publicação: 2023
Outros Autores: Albério, Carlos Augusto Abreu, Vieira, José Luiz Fernandes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Revista do Instituto de Medicina Tropical de São Paulo
Texto Completo: https://www.revistas.usp.br/rimtsp/article/view/218909
Resumo: Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.
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spelling Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosisTuberculosisIsoniazidInfectious diseasesDrug monitoringAntituberculosis drugsIsoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo2023-11-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/rimtsp/article/view/21890910.1590/S1678-9946202365056Revista do Instituto de Medicina Tropical de São Paulo; Vol. 65 (2023); e56Revista do Instituto de Medicina Tropical de São Paulo; v. 65 (2023); e56Revista do Instituto de Medicina Tropical de São Paulo; Vol. 65 (2023); e561678-99460036-4665reponame:Revista do Instituto de Medicina Tropical de São Pauloinstname:Instituto de Medicina Tropical (IMT)instacron:IMTenghttps://www.revistas.usp.br/rimtsp/article/view/218909/199952Copyright (c) 2023 Juan Gonzalo Bardalez Rivera, Carlos Augusto Abreu Albério, José Luiz Fernandes Vieirahttps://creativecommons.org/licenses/by-nc/4.0info:eu-repo/semantics/openAccessRivera, Juan Gonzalo Bardalez Albério, Carlos Augusto Abreu Vieira, José Luiz Fernandes 2023-12-20T14:25:40Zoai:revistas.usp.br:article/218909Revistahttp://www.revistas.usp.br/rimtsp/indexPUBhttps://www.revistas.usp.br/rimtsp/oai||revimtsp@usp.br1678-99460036-4665opendoar:2023-12-20T14:25:40Revista do Instituto de Medicina Tropical de São Paulo - Instituto de Medicina Tropical (IMT)false
dc.title.none.fl_str_mv Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
title Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
spellingShingle Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
Rivera, Juan Gonzalo Bardalez
Tuberculosis
Isoniazid
Infectious diseases
Drug monitoring
Antituberculosis drugs
title_short Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
title_full Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
title_fullStr Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
title_full_unstemmed Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
title_sort Influence of sex on the exposure to isoniazid in patients with pulmonary tuberculosis
author Rivera, Juan Gonzalo Bardalez
author_facet Rivera, Juan Gonzalo Bardalez
Albério, Carlos Augusto Abreu
Vieira, José Luiz Fernandes
author_role author
author2 Albério, Carlos Augusto Abreu
Vieira, José Luiz Fernandes
author2_role author
author
dc.contributor.author.fl_str_mv Rivera, Juan Gonzalo Bardalez
Albério, Carlos Augusto Abreu
Vieira, José Luiz Fernandes
dc.subject.por.fl_str_mv Tuberculosis
Isoniazid
Infectious diseases
Drug monitoring
Antituberculosis drugs
topic Tuberculosis
Isoniazid
Infectious diseases
Drug monitoring
Antituberculosis drugs
description Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-14
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/rimtsp/article/view/218909
10.1590/S1678-9946202365056
url https://www.revistas.usp.br/rimtsp/article/view/218909
identifier_str_mv 10.1590/S1678-9946202365056
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/rimtsp/article/view/218909/199952
dc.rights.driver.fl_str_mv https://creativecommons.org/licenses/by-nc/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
publisher.none.fl_str_mv Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
dc.source.none.fl_str_mv Revista do Instituto de Medicina Tropical de São Paulo; Vol. 65 (2023); e56
Revista do Instituto de Medicina Tropical de São Paulo; v. 65 (2023); e56
Revista do Instituto de Medicina Tropical de São Paulo; Vol. 65 (2023); e56
1678-9946
0036-4665
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reponame_str Revista do Instituto de Medicina Tropical de São Paulo
collection Revista do Instituto de Medicina Tropical de São Paulo
repository.name.fl_str_mv Revista do Instituto de Medicina Tropical de São Paulo - Instituto de Medicina Tropical (IMT)
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