{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:10:36Z","timestamp":1789726236404,"version":"4.0.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Ethambutol is used to treat tuberculosis (TB) in individuals living with HIV. Low concentrations of ethambutol have been reported in patients dosed with the World Health Organization (WHO)-recommended first-line regimen. We analyzed the pharmacokinetics of ethambutol in 61 HIV-positive individuals diagnosed with drug-sensitive TB enrolled in the tuberculosis and highly active antiretroviral therapy (TB-HAART) study. Participants started on TB treatment and were randomized to early or later introduction of efavirenz-based antiretroviral treatment. We explored potential covariate effects and evaluated the current WHO dosing recommendations for ethambutol in drug-susceptible and multidrug-resistant (MDR)-TB. A two-compartment model with first-order elimination allometrically scaled by fat-free mass and transit compartment absorption best described the pharmacokinetics of ethambutol. Clearance was estimated to be 40.3 L\/h for a typical individual with a fat-free mass (FFM) of 42 kg. The Antib-4 formulation had 26% higher bioavailability and slower mean transit time by 37% compared with Rifafour. Simulations showed that individuals in the lower weight bands (&lt;55 kg) who were administered ethambutol at WHO-recommended doses had relatively low drug exposures. These individuals would need doses of 825 mg if their body weight is &lt;37.9 kg and 1,100 mg if it is between 38 and 54.9 kg to achieve the reference maximum concentrations of 2\u20136 mg\/L and an area under the concentration-time curve (0\u201324) of 16\u201329 mg\u00b7h\/L. To achieve these targets in MDR-TB treatment, a dose increment of 400 mg (extra tablet) would be required for individuals in the lower weight band (&lt;46 kg). Our dose adjustments are consistent with the literature and can be recommended for consideration by the WHO for first-line drug-susceptible and MDR-TB treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01200-24","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:00:21Z","timestamp":1734962421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics of ethambutol and weight banded dosing in South African adults newly diagnosed with tuberculosis and HIV"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-341X","authenticated-orcid":true,"given":"Bonginkosi","family":"Ndzamba","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-079X","authenticated-orcid":true,"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0982-6226","authenticated-orcid":true,"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuli","family":"Mthiyane","sequence":"additional","affiliation":[{"name":"Clinical Operations Quality Management, IQVIA","place":["Centurion, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Rustomjee","sequence":"additional","affiliation":[{"name":"Strategic Health Innovation Partnerships (SHIP), South African Medical Research Council","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Onyebujoh","sequence":"additional","affiliation":[{"name":"Genetic Immunity Ltd.","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-8052","authenticated-orcid":true,"given":"Juan Eduardo","family":"Res\u00e9ndiz-Galv\u00e1n","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"2022. WHO consolidated guidelines on tuberculosis module 4: treatment drug-susceptible tuberculosis treatment. Available from: https:\/\/iris.who.int\/bitstream\/handle\/10665\/353829\/9789240048126-eng.pdf?sequence=1. Retrieved 30 May 2024."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics3030317"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02600-15"},{"key":"e_1_3_3_5_2","unstructured":"National center for biotechnology information. 2024. PubChem393 compound summary for CID 14051 ethambutol hydrochloride. Available from: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Ethambutol-Hydrochloride. 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Does AIDS impair the absorption of antituberculosis agents? Int J Tuberc Lung Dis 2:670\u2013675.","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03258-14"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1170-1177.2006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4473-4475.2004"},{"key":"e_1_3_3_25_2","unstructured":"South African national TB guidelines - adults. South African national TB guidelines - adults - UCT. 2017. 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