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A simpler once\u2010daily dosing schedule is critical to ensure patient\u2010friendly regimens with good adherence. We assessed expected drug exposures with proposed once\u2010daily doses for adults and compared novel model\u2010informed once\u2010daily dosing strategies for children with current World Health Organization (WHO) recommended dosing. A reference individual and virtual pediatric population were generated to simulate exposures in adults and children, respectively. Published population models characterizing the exposures of bedaquiline and its metabolite M2, delamanid, and its metabolite DM\u20106705 were utilized. During simulation, child growth during treatment along with several CYP3A4 ontogeny profiles was accounted for. Exposures in children were compared with simulated adult targets to assess the expected treatment efficacy and safety. In adults, the proposed bedaquiline once\u2010daily dosing (400\u2009mg daily for 2\u2009weeks followed by 100\u2009mg daily for 22\u2009weeks) yielded 14% higher exposures of bedaquiline and M2 compared to the labeled dosing scheme at 24\u2009weeks; for delamanid and DM\u20106705, the suggested 300 mg daily dose provided 13% lower exposures at steady state. For children, the cumulative proportions of exposures of both drugs showed &lt;\u20095% difference between WHO\u2010recommended and proposed once\u2010daily dosing. This study demonstrated the use of model\u2010informed approaches to propose rational and simpler regimens for bedaquiline and delamanid in adults and children. The new once\u2010daily dosing strategies will be tested in the PARADIGM4TB and IMPAACT 2020 trials in adults and children, respectively.<\/jats:p>","DOI":"10.1002\/cpt.3536","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T08:06:43Z","timestamp":1735373203000},"page":"1292-1302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Model\u2010Informed Once\u2010Daily Dosing Strategy for Bedaquiline and Delamanid in Children, Adolescents and Adults with Tuberculosis"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7501-5326","authenticated-orcid":false,"given":"Yu\u2010Jou","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-7477","authenticated-orcid":false,"given":"Louvina E.","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Desmond Tutu TB Centre Stellenbosch University  Stellenbosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-1950","authenticated-orcid":false,"given":"Anthony J.","family":"Garcia\u2010Prats","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Desmond Tutu TB Centre Stellenbosch University  Stellenbosch South Africa"},{"name":"Department of Pediatrics University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-9834","authenticated-orcid":false,"given":"Anneke C.","family":"Hesseling","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Desmond Tutu TB Centre Stellenbosch University  Stellenbosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-6445","authenticated-orcid":false,"given":"Elin M.","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"},{"name":"Department of Pharmacy Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"World Health Organization.Global tuberculosis report 2023. <https:\/\/iris.who.int\/bitstream\/handle\/10665\/373828\/9789240083851\u2010eng.pdf> (2023). 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