{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:40:17Z","timestamp":1790782817084,"version":"4.1.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020193","name":"Novartis Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020193","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We described the pharmacokinetics and safety of clofazimine in children treated for multidrug\/rifampicin-resistant tuberculosis (MDR\/RR-TB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children aged &amp;lt;18 years were eligible. Clofazimine was administered by weight-based dosing. Sparse and semi-intensive pharmacokinetic sampling was completed at baseline and weeks 2 and 16. Clofazimine weekly area under the concentration time-curve (wAUC) was compared with the target wAUC (60.87\u2005mg \u00d7 h\/L and 111.79\u2005mg \u00d7 h\/L) in adults receiving clofazimine (100\u2005mg) daily for MDR\/RR-TB and leprosy, respectively. Safety monitoring included measurement of QT interval prolongation and laboratory assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty children were included: median age was 6.0 years (IQR, 1.6\u201314.4); 6 (30%) were male. Median clofazimine wAUC was 162.94 (IQR, 130.06\u2013263.95), &amp;gt;25% higher than the target adult wAUC in adults with MDR\/RR-TB (111.79; IQR, 81.9\u2013151.9). No serious or grade \u22653 cardiac events occurred. There was a QT interval increase of 0.02\u2005milliseconds for every 1-\u00b5g\/L increase in clofazimine concentration. One severe adverse event (elevated alanine transferase) led to temporary withdrawal of clofazimine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The clofazimine doses used achieved substantially higher exposures in children than adults receiving standard clofazimine doses. The association of higher clofazimine exposures and QT interval prolongation may pose unnecessary risk to children, particularly in combination with other QT-prolonging drugs.<\/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\/jiaf057","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T23:22:55Z","timestamp":1739229775000},"page":"e873-e881","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics and Safety of Clofazimine in Children With Rifampicin-Resistant Tuberculosis"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-9509","authenticated-orcid":false,"given":"Jennifer A","family":"Hughes","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\/0000-0003-4621-5480","authenticated-orcid":false,"given":"Bel\u00e9n P","family":"Solans","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine"},{"name":"UCSF Center for Tuberculosis, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather R","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":"H Simon","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":"James C","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hassenfeld Children's Hospital at NYU Langone , New York , New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elri","family":"Nortier","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"}]},{"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 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