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We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp\/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance.\n              <jats:italic>A posteriori<\/jats:italic>\n              power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at\n              <jats:italic>P<\/jats:italic>\n              &lt; 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01583-23","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T13:00:36Z","timestamp":1712754036000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Assessing potential drug-drug interactions between clofazimine and other frequently used agents to treat drug-resistant tuberculosis"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5084-4314","authenticated-orcid":false,"given":"Allan","family":"Kengo","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South 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Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattamukkil","family":"Abraham","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubbe","family":"Weisner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modiehi Helen","family":"Mosala","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibongile","family":"Tshabalala","sequence":"additional","affiliation":[{"name":"Bioengineering and Integrated Genomics Group, Council for Scientific and Industrial Research, Pretoria, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Scholefield","sequence":"additional","affiliation":[{"name":"Bioengineering and Integrated Genomics Group, Council for Scientific and Industrial Research, Pretoria, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-8052","authenticated-orcid":false,"given":"Juan Eduardo","family":"Resendiz-Galvan","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Martinson","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa"},{"name":"Johns Hopkins University Center for Tuberculosis Research, Division of Infectious Diseases, School of 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