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Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.

التفاصيل البيبلوغرافية
العنوان: Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.
المؤلفون: Beraldi-Magalhaes F; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil.; Secretaria de Estado da Saúde do Paraná, Curitiba 80010-130, Brazil.; School of Medicine, Faculdades Pequeno Príncipe, Curitiba 80230-020, Brazil., Parker SL; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia., Sanches C; Department of Pharmacy, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João del-Rei, Divinopolis 35501-296, Brazil., Garcia LS; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil., Souza Carvalho BK; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil., Costa AA; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil., Fachi MM; Department of Pharmacy, Campus Jardim Botânico, Universidade Federal do Paraná, Curitiba 80210-170, Brazil., de Liz MV; Department of Chemistry & Biology, Campus Curitiba, Universidade Tecnológica Federal do Paraná, Curitiba 81280-340, Brazil., de Souza AB; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil., Safe IP; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil., Pontarolo R; Department of Pharmacy, Campus Jardim Botânico, Universidade Federal do Paraná, Curitiba 80210-170, Brazil., Wallis S; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia., Lipman J; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia.; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, 30900 Nimes, France., Roberts JA; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia.; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, 30900 Nimes, France.; Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia., Cordeiro-Santos M; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil.; Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil.; School of Medicine, Universidade Nilton Lins, Manaus 69058-040, Brazil.
المصدر: Tropical medicine and infectious disease [Trop Med Infect Dis] 2023 Jun 08; Vol. 8 (6). Date of Electronic Publication: 2023 Jun 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101709042 Publication Model: Electronic Cited Medium: Internet ISSN: 2414-6366 (Electronic) Linking ISSN: 24146366 NLM ISO Abbreviation: Trop Med Infect Dis Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2016]-
مستخلص: Background: Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality.
Methods: A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis.
Results: Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients.
Conclusions: ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.
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معلومات مُعتمدة: 001 Coordenação de Aperfeicoamento de Pessoal de Nível Superior; 002/2018; 005/2019; 004/2020 Fundação de Amparo à Pesquisa do Estado do Amazonas; APP1142757 National Health and Medical Research Council-funded Fellowship; APP1044941 National Health and Medical Research Council-funded Centre for Research Excellence
فهرسة مساهمة: Keywords: antitubercular agents; biological availability; critical care; ethambutol; intensive care; isoniazid; pharmacokinetics; pyrazinamide; rifampin; tuberculosis
تواريخ الأحداث: Date Created: 20230627 Latest Revision: 20230701
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10303681
DOI: 10.3390/tropicalmed8060312
PMID: 37368730
قاعدة البيانات: MEDLINE
الوصف
تدمد:2414-6366
DOI:10.3390/tropicalmed8060312