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Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations

Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatmen...

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Autores principales: Cheng, Lin, Luo, Ming, Guo, Yan, Fan, Yunfan, Wang, Pengsen, Zhou, Gang, Qin, Shiwei, Weng, Bangbi, Li, Peibo, Liu, Zhirui, Liu, Songtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587680/
https://www.ncbi.nlm.nih.gov/pubmed/37869746
http://dx.doi.org/10.3389/fphar.2023.1248331
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author Cheng, Lin
Luo, Ming
Guo, Yan
Fan, Yunfan
Wang, Pengsen
Zhou, Gang
Qin, Shiwei
Weng, Bangbi
Li, Peibo
Liu, Zhirui
Liu, Songtao
author_facet Cheng, Lin
Luo, Ming
Guo, Yan
Fan, Yunfan
Wang, Pengsen
Zhou, Gang
Qin, Shiwei
Weng, Bangbi
Li, Peibo
Liu, Zhirui
Liu, Songtao
author_sort Cheng, Lin
collection PubMed
description Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs.
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spelling pubmed-105876802023-10-21 Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations Cheng, Lin Luo, Ming Guo, Yan Fan, Yunfan Wang, Pengsen Zhou, Gang Qin, Shiwei Weng, Bangbi Li, Peibo Liu, Zhirui Liu, Songtao Front Pharmacol Pharmacology Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs. Frontiers Media S.A. 2023-10-06 /pmc/articles/PMC10587680/ /pubmed/37869746 http://dx.doi.org/10.3389/fphar.2023.1248331 Text en Copyright © 2023 Cheng, Luo, Guo, Fan, Wang, Zhou, Qin, Weng, Li, Liu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cheng, Lin
Luo, Ming
Guo, Yan
Fan, Yunfan
Wang, Pengsen
Zhou, Gang
Qin, Shiwei
Weng, Bangbi
Li, Peibo
Liu, Zhirui
Liu, Songtao
Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title_full Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title_fullStr Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title_full_unstemmed Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title_short Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
title_sort correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587680/
https://www.ncbi.nlm.nih.gov/pubmed/37869746
http://dx.doi.org/10.3389/fphar.2023.1248331
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