{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:13:40Z","timestamp":1760148820435,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"],"award-info":[{"award-number":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brasil (CAPES)\u2014Finance Code 001 and by Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas (FAPEAM)","award":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"],"award-info":[{"award-number":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"]}]},{"name":"National Health and Medical Research Council-funded Centre of Research Excellence","award":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"],"award-info":[{"award-number":["001","N.005\/2022","#002\/2008","#005\/2019","#004\/2020","APP2007007","APP2009736"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/tropicalmed8060312","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:03:18Z","timestamp":1686276198000},"page":"312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0944-3321","authenticated-orcid":false,"given":"Francisco","family":"Beraldi-Magalhaes","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil"},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"},{"name":"Secretaria de Estado da Sa\u00fade do Paran\u00e1, Curitiba 80010-130, Brazil"},{"name":"School of Medicine, Faculdades Pequeno Pr\u00edncipe, Curitiba 80230-020, Brazil"}]},{"given":"Suzanne L.","family":"Parker","sequence":"additional","affiliation":[{"name":"UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-1337","authenticated-orcid":false,"given":"Cristina","family":"Sanches","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Campus Centro-Oeste Dona Lindu, Universidade Federal de S\u00e3o Jo\u00e3o del-Rei, Divinopolis 35501-296, Brazil"}]},{"given":"Leandro Sousa","family":"Garcia","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil"},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"}]},{"given":"Brenda Karoline","family":"Souza Carvalho","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil"},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"}]},{"given":"Amanda Araujo","family":"Costa","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"}]},{"given":"Mariana Millan","family":"Fachi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Campus Jardim Bot\u00e2nico, Universidade Federal do Paran\u00e1, Curitiba 80210-170, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-3365","authenticated-orcid":false,"given":"Marcus Vinicius","family":"de Liz","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biology, Campus Curitiba, Universidade Tecnol\u00f3gica Federal do Paran\u00e1, Curitiba 81280-340, Brazil"}]},{"given":"Alexandra Brito","family":"de Souza","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil"},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"}]},{"given":"Izabella Picinin","family":"Safe","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7049-4363","authenticated-orcid":false,"given":"Roberto","family":"Pontarolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Campus Jardim Bot\u00e2nico, Universidade Federal do Paran\u00e1, Curitiba 80210-170, Brazil"}]},{"given":"Steven","family":"Wallis","sequence":"additional","affiliation":[{"name":"UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-9876","authenticated-orcid":false,"given":"Jeffrey","family":"Lipman","sequence":"additional","affiliation":[{"name":"UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia"},{"name":"Department of Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital, Brisbane, QLD 4029, Australia"},{"name":"Division of Anaesthesiology Critical Care Emergency and Pain Medicine, N\u00eemes University Hospital, University of Montpellier, 30900 Nimes, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-435X","authenticated-orcid":false,"given":"Jason A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia"},{"name":"Department of Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital, Brisbane, QLD 4029, Australia"},{"name":"Division of Anaesthesiology Critical Care Emergency and Pain Medicine, N\u00eemes University Hospital, University of Montpellier, 30900 Nimes, France"},{"name":"Department of Pharmacy, Royal Brisbane and Women\u2019s Hospital, Brisbane, QLD 4029, Australia"}]},{"given":"Marcelo","family":"Cordeiro-Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, Brazil"},{"name":"Funda\u00e7\u00e3o de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus 69040-000, Brazil"},{"name":"School of Medicine, Universidade Nilton Lins, Manaus 69058-040, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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