{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:37Z","timestamp":1793325757740,"version":"4.5.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,11,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      SPR720 is a phosphate ester prodrug that is converted rapidly\n                      <jats:italic>in vivo<\/jats:italic>\n                      to SPR719, the active moiety, which exhibits potent\n                      <jats:italic>in vitro<\/jats:italic>\n                      activity against clinically relevant mycobacterial species including\n                      <jats:italic>Mycobacterium avium<\/jats:italic>\n                      complex (MAC) and\n                      <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                      . SPR720 is in clinical development for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) due to MAC. This study evaluated the safety and the intrapulmonary pharmacokinetics of SPR719 in healthy volunteers. A total of 30 subjects received oral SPR720 1,000 mg once daily for 7 days followed by bronchoscopy and bronchoalveolar lavage, with blood samples collected for plasma pharmacokinetic assessments. Mean SPR719 area under the concentration-time curve from time 0 to 24 hours (AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      ) and maximum concentration (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) for plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) were 52,418 ng\u00b7h\/mL and 4,315 ng\/mL, 59,880 ng\u00b7h\/mL and 5,429 ng\/mL, and 128,105 ng\u00b7h\/mL and 13,033 ng\/mL, respectively. The ratios of ELF to total plasma concentrations of SPR719 based on AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      were 1.14 and 1.26, and the ratios of AM to total plasma concentrations of SPR719 based on AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      were 2.44 and 3.02, respectively. When corrected for protein binding, the ratios of ELF to unbound plasma concentrations of SPR719 for AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      were 19.87 and 21.88, and the ratios of AM to unbound plasma concentrations of SPR719 for AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      were 42.50 and 52.53, respectively. No unexpected safety findings were observed. Results from this study of the intrapulmonary disposition of SPR719 support further investigation of SPR720 as a potential oral agent for the treatment of patients with NTM-PD.\n                    <\/jats:p>\n                    <jats:p>\n                      This study is registered with\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">Clinicaltrials.gov<\/jats:ext-link>\n                      as\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05955586\" xlink:type=\"simple\">NCT05955586<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01103-24","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T09:00:20Z","timestamp":1727773220000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Intrapulmonary pharmacokinetics of SPR719 following oral administration of SPR720 to healthy volunteers"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-7346","authenticated-orcid":true,"given":"Keith A.","family":"Rodvold","sequence":"first","affiliation":[{"name":"University of Illinois Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Gotfried","sequence":"additional","affiliation":[{"name":"Pulmonary Associates, PA, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilla T.","family":"Ussery","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekman L.","family":"Wong","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-9736","authenticated-orcid":true,"given":"Kamal A.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Lung nontuberculous mycobacterial infections","author":"Bethencourt Mirabal A","year":"2024","unstructured":"Bethencourt Mirabal A, Nguyen AD, Ferrer G. 2024. Lung nontuberculous mycobacterial infections. 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