{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:40Z","timestamp":1785418540095,"version":"3.56.0"},"reference-count":11,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Beijing Municipal Health Commission Dengfeng Program","award":["G202511062"],"award-info":[{"award-number":["G202511062"]}]},{"name":"Beijing Municipal Health Commission Excellent Clinical Research Program for Research-Oriented Wards","award":["BRWEP2024W042160109"],"award-info":[{"award-number":["BRWEP2024W042160109"]}]},{"name":"Beijing Tongzhou District Science and Technology Program Project","award":["WS2024017"],"award-info":[{"award-number":["WS2024017"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      To examine the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      distribution of WX-081 alone or in combination with clarithromycin (Clr) or clofazimine (CFZ) in rats infected with\n                      <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                      and evaluate the effects of the interactions of WX-081 with Clr and CFZ on its tissue distribution, the concentrations of WX-081 in plasma, brain, vertebral, and lung tissue of Sprague-Dawley rats at 20 min, 1 h, and 16 h post-treatment with 45 mg\/kg WX-081 (Group A), 45 mg\/kg WX-081 plus 10 mg\/kg Clr (Group B), or 45 mg\/kg WX-081 plus 25 mg\/kg CFZ (Group C) were determined by liquid chromatography-tandem mass spectrometry. Differences between continuous variables were analyzed using Student\u2019s\n                      <jats:italic toggle=\"yes\">t<\/jats:italic>\n                      -test (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2264 0.05). At 20 min, rats in groups B and C had higher plasma WX-081 concentration than those in Group A (458.7 ng\/mL vs. 140.4 ng\/mL,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.012; 351.7 ng\/mL vs. 140.4 ng\/mL,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.022, respectively). At 1 h, only Group B had a higher plasma level than Group A (2,522.3 ng\/mL vs. 1,413.2 ng\/mL, respectively,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.018), while the WX-081 concentration in Group B lung tissue exceeded that in Group A lung tissue (8,890.9 ng\/g vs. 6,666.8 ng\/g, respectively,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.041), and that of Group C lungs was lower than that of Group A lung tissue (3,953.4 ng\/g vs. 6,666.8 ng\/g, respectively,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.014). The lung tissue consistently had the highest WX-081 concentration at all time points. At 20 min, plasma WX-081 levels in groups B and C surpassed that of Group A. At 1 h, Group B had higher plasma and lung WX-081 concentration, while Group C had a lower lung WX-081 concentration than Group A.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The study pioneers the exploration of WX-081\u2019s\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        distribution and drug interactions with Clr or CFZ in a rat\n                        <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                        infection model. It shows that co-administration alters tissue distribution, boosting lung concentrations\u2014key for treating pulmonary infections. These insights guide regimen optimization and underscore WX-081\u2019s potential as a safer alternative, enhancing treatment for non-tuberculous mycobacterial diseases.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01555-25","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:00:32Z","timestamp":1772114432000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Increasing\n                    <i>in vivo<\/i>\n                    drug exposure levels of compound WX-081 (sudapyridine) when used in combination with clofazimine or clarithromycin"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3684-3861","authenticated-orcid":false,"given":"Xueyu","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-7321","authenticated-orcid":true,"given":"Xia","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongguo","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Jiatan Pharmatech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Jiatan Pharmatech Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naihui","family":"Chu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4295-4262","authenticated-orcid":true,"given":"Hairong","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1109-1983","authenticated-orcid":true,"given":"Wenjuan","family":"Nie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00250-2019"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.10.013"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"},{"key":"e_1_3_5_5_2","unstructured":"Rapid communication: key changes to treatment of multidrug- and rifampicin-resistant tuberculosis (MDR\/RR-TB). 2018. Geneva World Health Organization"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky526"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.06.004"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2022.128824"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02477-21"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01372-22"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1217975"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1115530"}],"container-title":["Microbiology Spectrum"],"original-title":[],"contributor":[{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]}],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01555-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01555-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T13:09:30Z","timestamp":1775567370000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01555-25"}},"subtitle":[],"editor":[{"given":"Valeria","family":"Allizond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,7]]}},"alternative-id":["10.1128\/spectrum.01555-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01555-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2025-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01555-25"}}