{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:21:17Z","timestamp":1790220077924,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antileprosy drug clofazimine has shown potential for shortening tuberculosis treatment; however, the current dosing of the drug is not evidence based, and the optimal dosing is unknown. Our objective was to conduct a preclinical evaluation of the pharmacokinetics and pharmacodynamics of clofazimine in the mouse model of tuberculosis, with the goal of providing useful information on dosing for future studies. Pharmacokinetic parameters were evaluated in infected and uninfected BALB\/c mice. Pharmacodynamic parameters were evaluated in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            -infected mice that were treated for 12 weeks with one of six different clofazimine dosing regimens, i.e., doses of 6.25, 12.5, and 25 mg\/kg of body weight\/day and 3 regimens with loading doses. Clofazimine progressively accumulated in the lungs, livers, and spleens of the mice, reaching levels of greater than 50 \u03bcg\/g in all tissues by 4 weeks of administration, while serum drug levels remained low at 1 to 2 \u03bcg\/ml. Elimination of clofazimine was extremely slow, and the half-life was dependent on the duration of drug administration. Clofazimine exhibited dose-dependent tissue and serum concentrations. At any dose, clofazimine did not have bactericidal activity during the first 2 weeks of administration but subsequently demonstrated potent, dose-independent bactericidal activity. The antituberculosis activity of clofazimine was dependent on neither the dose administered nor the drug concentrations in the tissues, suggesting that much lower doses could be effectively used for tuberculosis treatment.\n          <\/jats:p>","DOI":"10.1128\/aac.00260-15","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T02:03:07Z","timestamp":1425952987000},"page":"3042-3051","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["Pharmacokinetics and Pharmacodynamics of Clofazimine in a Mouse Model of Tuberculosis"],"prefix":"10.1128","volume":"59","author":[{"given":"Rosemary V.","family":"Swanson","sequence":"first","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adamson","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chivonne","family":"Moodley","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. 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