{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:19:02Z","timestamp":1791901142847,"version":"4.3.4"},"reference-count":19,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Clofazimine inhalation suspension is a novel formulation of clofazimine developed as a potential lung-targeted treatment for pulmonary nontuberculous mycobacteria disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Safety and toxicokinetic parameters were assessed in 28-day, repeat-dose studies of up to 3.59 mg\/kg\/day clofazimine inhalation suspension in 8-week-old Sprague Dawley rats and up to 2.72 mg\/kg\/day in 5\u20137-month-old beagle dogs with 56-day recovery periods. A 6-month inhalation toxicity study without recovery was also conducted in beagle dogs, with daily doses up to 2.95 mg\/kg for 182 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>No adverse effects were observed, but minimal to mild nonadverse pulmonary changes were observed in high-dose treatment groups. The no-observed-adverse-effect levels were a sex-averaged 1.78 mg\/kg in rats (28 days) and 2.73\/2.95 mg\/kg in male\/female dogs (182 days). Median time to maximum concentration ranged from 6 to 12 hours and 0.5 to 6 hours in the rat and dog studies, respectively. Plasma area under the concentration\u2013time curve from 0 to 24 hours and maximum plasma concentration increased dose-dependently and exhibited accumulation ratios \u2265\u223c2 in both 28-day studies. Clofazimine concentrations in lung tissue were dose-dependent in all 3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>\n                      Clofazimine inhalation suspension was well tolerated at doses supporting multifold safety margins for the ongoing phase 3 ICoN-1 study. Lung concentrations exceeded the estimated minimum inhibitory concentration against\n                      <jats:italic toggle=\"yes\">Mycobacterium avium<\/jats:italic>\n                      complex, even after 56 days of recovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19412711251389444","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T16:33:18Z","timestamp":1761323598000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Preclinical Studies of Clofazimine Inhalation Suspension: A Novel Formulation for the Treatment of Pulmonary Nontuberculous Mycobacterial Disease"],"prefix":"10.1177","volume":"39","author":[{"given":"Wassim H.","family":"Fares","sequence":"first","affiliation":[{"name":"MannKind, Danbury, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Castagna","sequence":"additional","affiliation":[{"name":"MannKind, Danbury, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hofmann","sequence":"additional","affiliation":[{"name":"MannKind, Danbury, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-678OC"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3113-x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2017.1386563"},{"key":"e_1_3_3_5_2","volume-title":"LAMPRENE\u00ae (clofazimine capsule for oral use).","author":"Novartis","year":"2019","unstructured":"Novartis. LAMPRENE\u00ae (clofazimine capsule for oral use). Full Prescribing Information. Novartis Pharmaceuticals Corporation; 2019."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01144-22"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.05.013"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.cgd.6b01411"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/08958370802207318"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1091581815624080"},{"issue":"1","key":"e_1_3_3_11_2","first-page":"9","article-title":"Pharmacokinetics of clofazimine in healthy volunteers","volume":"55","author":"Schaad-Lanyi Z","year":"1987","unstructured":"Schaad-Lanyi Z, , Dieterle W, , Dubois JP, et al. Pharmacokinetics of clofazimine in healthy volunteers. Int J Lepr Other Mycobact Dis, 1987; 55(1):9\u201315.","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.7b00521"},{"key":"e_1_3_3_13_2","unstructured":"SIELC Technologies. Fluticasone propionate. Available from: https:\/\/sielc.com\/fluticasone-propionate [Last accessed: August11 2025]."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-6749(98)70156-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0570-0"},{"key":"e_1_3_3_16_2","volume-title":"NebuPent (pentamidine isethionate). Full Prescribing Information","author":"APP Pharmaceuticals, LLC","year":"2010","unstructured":"APP Pharmaceuticals, LLC. NebuPent (pentamidine isethionate). Full Prescribing Information. APP Pharmaceuticals, LLC; 2010."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00260-15"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01731-12"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad317"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"}],"container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19412711251389444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19412711251389444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19412711251389444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:16:17Z","timestamp":1777900577000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19412711251389444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4,1]]}},"alternative-id":["10.1177\/19412711251389444"],"URL":"https:\/\/doi.org\/10.1177\/19412711251389444","relation":{},"ISSN":["1941-2711","1941-2703"],"issn-type":[{"value":"1941-2711","type":"print"},{"value":"1941-2703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]}}}