{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:19:12Z","timestamp":1791901152275,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Clofazimine is a promising drug for the treatment of nontuberculous mycobacterial (NTM) diseases. Accumulation of clofazimine to reach steady-state plasma concentrations takes months. A loading dose may reduce the time to steady-state-like concentrations. We evaluated the pharmacokinetics (PK), safety and tolerability of a loading dose regimen in patients with NTM disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult participants received a 4-week loading dose regimen of 300\u2005mg clofazimine once daily, followed by a maintenance dose of 100\u2005mg once daily (combined with other antimycobacterial drugs). Blood samples for PK analysis were collected on three occasions. A population PK model for clofazimine was developed and simulations were performed to assess the time to reach steady-state-like (target) concentrations for different dosing regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twelve participants were included. The geometric mean peak and trough clofazimine concentrations after the 4-week loading phase were 0.87 and 0.50\u2005mg\/L, respectively. Adverse events were common, but mostly mild and none led to discontinuation of clofazimine. Our loading dose regimen reduced the predicted median time to target concentrations by 1.5\u2005months compared to no loading dose (3.8 versus 5.3\u2005months). Further time benefit was predicted with a 6-week loading dose regimen (1.4 versus 5.3\u2005months).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A 4-week loading dose regimen of 300\u2005mg once daily reduced the time to target clofazimine concentrations and was safe and well-tolerated. Extending the loading phase to 6 weeks could further decrease the time to target concentrations. Using a loading dose of clofazimine is a feasible strategy to optimize treatment of NTM disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT05294146<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae309","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:56:49Z","timestamp":1728410209000},"page":"3100-3108","source":"Crossref","is-referenced-by-count":18,"title":["A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6912-4163","authenticated-orcid":false,"given":"Ralf","family":"Stemkens","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen 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Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey H M","family":"te Brake","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-6410","authenticated-orcid":false,"given":"Reinout","family":"van Crevel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Infectious Diseases, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J","family":"Boeree","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen 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