{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:18Z","timestamp":1786602438215,"version":"build-2736575974"},"reference-count":20,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNITAID\u2019s"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clofazimine is commonly included in multidrug regimens for children with multidrug-resistant and rifampicin-resistant tuberculosis (MDR\/RR-TB), but accurate pediatric dosing has been limited by 100-mg soft-gel capsules that cannot be reliably divided. We evaluated the exposure and safety of a novel 50-mg clofazimine tablet using revised once-daily weight-banded dosing informed by a previous study (Clofazimine PK1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children &amp;lt;18 years weighing &amp;lt;30\u2005kg receiving MDR\/RR-TB treatment, including clofazimine, were enrolled. Sparse and semi-intensive pharmacokinetic sampling was completed at baseline and at weeks 2 and 12. Model-predicted weekly steady-state area-under-the-curve (wAUCss) was compared with an adult target of 111.79\u2005mg\u00b7h\/L. Safety monitoring included clinical, laboratory, and electrocardiogram (ECG) monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve children were included (median age 2.8 years; range 0.6\u20138.2). Median predicted wAUCss was 106\u2005mg\u00b7h\/L (range 76.9\u2013274), within 25% of target. Two grade 3 adverse events (drug-induced liver injury and skin hyperpigmentation) possibly related to clofazimine, but no other clofazimine-related serious adverse events, were observed, The Fridericia corrected QT (QTcF) interval typically increased with 0.042\u2005ms per1-\u00b5g\/L increase in clofazimine concentration; five QTcF prolongations (&amp;gt;460\u2013480\u2005ms) occurred in three participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The revised once-daily dosing with the 50-mg clofazimine tablet achieved the predefined exposure target. Clinically important adverse events support cautious use with ECG and laboratory monitoring and further evaluation before broad adoption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>South African National Clinical Trials Register (https:\/\/sanctr.samrc.ac.za\/; DOH-27-0620-6415).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag381","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:09:12Z","timestamp":1786100952000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Safety of a Novel Clofazimine Formulation and Dosing Strategy in Children With Rifampicin-resistant Tuberculosis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7362-9962","authenticated-orcid":false,"given":"Elri","family":"Nortier","sequence":"first","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2403-6846","authenticated-orcid":false,"given":"Milena M","family":"Boczar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-9509","authenticated-orcid":false,"given":"Jennifer A","family":"Hughes","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6144-4989","authenticated-orcid":false,"given":"Joh-Nell","family":"van der Westhuizen","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-2483","authenticated-orcid":false,"given":"Megan","family":"Palmer","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-1950","authenticated-orcid":false,"given":"Anthony J","family":"Garcia-Prats","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin , Madison, Wisconsin ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-7477","authenticated-orcid":false,"given":"Louvina","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hassenfeld Children's Hospital at NYU Langone , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1258-8297","authenticated-orcid":false,"given":"Mats O","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelaide","family":"Carelse","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Courtney","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Draper","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-4133","authenticated-orcid":false,"given":"Hendrik S","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Faraj","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin M","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]},{"name":"Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-9834","authenticated-orcid":false,"given":"Anneke C","family":"Hesseling","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South 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