{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:49:40Z","timestamp":1790887780084,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bedaquiline is approved for use in a thrice\u2010weekly dosing schedule; simpler once\u2010daily dosing strategies could enable fixed\u2010dose combinations and improve patient adherence. We developed an interactive R Shiny simulation tool to enable the evaluation of different bedaquiline dosing schedules within an integrated dose\u2010pharmacokinetic\u2010efficacy\u2010safety\u2010outcome framework. Four models describing bedaquiline and its metabolite M2 concentrations, time\u2010to\u2010positivity sputum culture results, QTc intervals, and long\u2010term outcomes were incorporated in the framework. A virtual population representative of tuberculosis patients was generated for simulation. Two case studies were investigated: (1) alternative bedaquiline dosing regimens and (2) bedaquiline treatment interruption and reinitiation. The ZeNix once\u2010daily dosing (200\u2009mg once daily for 8\u2009weeks, followed by 100\u2009mg once daily for 16\u2009weeks) yielded 50% lower median bedaquiline and M2 weekly average concentrations compared to the registered (approved) and standard\u2010loading once\u2010daily dosing (400\u2009mg once daily for 2\u2009weeks, followed by 100\u2009mg once daily for 22\u2009weeks) at 2\u2009weeks. The exposure difference was predicted to lead to 11% fewer patients with negative cultures at 2\u2009weeks and 5.8% fewer patients having sputum culture conversions at 8\u2009weeks under the ZeNix dosing. The QTcF intervals were predicted from 376 to 442\u2009ms (5th to 95th percentile of the population) for the three evaluated strategies. We also demonstrated that the Shiny application could guide decisions on the timing and doses for reloading bedaquiline after treatment interruption. The developed Shiny platform supports future exploration of bedaquiline treatment under different scenarios, for example, potential drug\u2013drug interactions and clinical trial simulations.<\/jats:p>","DOI":"10.1002\/psp4.70264","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T13:52:08Z","timestamp":1778593928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Interactive Pharmacokinetic\u2010Pharmacodynamic Framework to Evaluate Bedaquiline Dose Modifications in Adults With Tuberculosis"],"prefix":"10.1002","volume":"15","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Okibedi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"},{"name":"Department of Clinical Pharmacy &amp; Biochemistry, Institute of Pharmacy Freie Universitaet Berlin  Berlin Germany"}],"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 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.54394\/CJQU6666"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix362"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00391-2019"},{"issue":"6","key":"e_1_2_9_5_1","article-title":"Tuberculosis Infectiousness and Host Susceptibility","volume":"216","author":"Turner R. 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