{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:57:07Z","timestamp":1774339027141,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"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 Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["002\/2008"],"award-info":[{"award-number":["002\/2008"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["005\/2019"],"award-info":[{"award-number":["005\/2019"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. Methods: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC\/MIC &gt; 11.9 and Cmax\/MIC &gt; 0.48 values. Optimized dosing regimens were simulated at steady state. Results: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p &lt; 0.05). Mean bioavailability for ICU patients was &gt;5-times higher than outpatients (p &lt; 0.0001). Clearance and volume of distribution were 93% (p &lt; 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. Conclusions: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.<\/jats:p>","DOI":"10.3390\/antibiotics10121559","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"1559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study"],"prefix":"10.3390","volume":"10","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, Universidade Federal de S\u00e3o Jo\u00e3o del-Rei, Divinopolis 35501-296, Brazil"}]},{"given":"Leandro","family":"Sousa 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":"Mariana Millan","family":"Fachi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Universidade Federal do Paran\u00e1, Curitiba 80210-170, Brazil"}]},{"given":"Marcus Vinicius","family":"de Liz","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology, Universidade Federal Tecnol\u00f3gica do Paran\u00e1, Curitiba 81280-340, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7049-4363","authenticated-orcid":false,"given":"Roberto","family":"Pontarolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Universidade Federal do Paran\u00e1, Curitiba 80210-170, Brazil"}]},{"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"}]},{"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"}]},{"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"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020). 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