{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T02:12:57Z","timestamp":1770689577750,"version":"3.49.0"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"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":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Solithromycin, a novel macrolide and the first fluoroketolide, is being developed as a therapy for community-acquired bacterial pneumonia, with a distinct mechanism that provides activity against macrolide-resistant bacteria. The pharmacokinetics, metabolism, and excretion of solithromycin were studied in healthy male subjects after oral administration of a single 800-mg (\u223c100-\u03bcCi) dose of [\n            <jats:sup>14<\/jats:sup>\n            C]solithromycin. Solithromycin was well tolerated, and absorption from the solution occurred with a median time to peak concentration of 4.0 h. Solithromycin and the total radioactivity had similar profiles with no long-lived metabolites. The whole-blood total radioactivity was approximately 75% of the plasma total radioactivity. Recovery was essentially complete (mean, 90.6%), with 76.5% and 14.1% of the dose recovered in feces and urine, respectively. Unchanged solithromycin (CEM-101) was the predominant circulating radioactive component in plasma (77% of the total radioactivity area under the concentration-time curve [AUC]), with two minor plasma metabolites, CEM-214 and CEM-122 (\n            <jats:italic>N<\/jats:italic>\n            -acetyl-CEM-101), each accounting for approximately 5% of the total radioactivity. Urinary excretion was predominantly like that of the parent. Solithromycin was primarily eliminated in the feces after extensive metabolism via a complex metabolic pathway with CEM-262 as the major constituent (27.36% of the administered dose). Overall oxidative pathways, presumably carried out mostly by CYP3A4, represented the majority of the metabolism, with\n            <jats:italic>N<\/jats:italic>\n            -acetylation present to a lesser extent. No disproportionate human metabolites were observed.\n          <\/jats:p>","DOI":"10.1128\/aac.01474-17","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T11:10:40Z","timestamp":1519816240000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Metabolism, Excretion, and Mass Balance of Solithromycin in Humans"],"prefix":"10.1128","volume":"62","author":[{"given":"Christopher","family":"MacLauchlin","sequence":"first","affiliation":[{"name":"Cempra Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen E.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Cempra Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara","family":"Keedy","sequence":"additional","affiliation":[{"name":"Cempra Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prabhavathi","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Cempra Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian D.","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Cempra Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001474"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.129502"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00185-16"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.01.035"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00860-10"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw490"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00017-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw428"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2016.137"},{"key":"e_1_3_3_11_2","first-page":"29","volume-title":"New antibacterial discovery and development","author":"Schneider S","year":"2014","unstructured":"Schneider S, Pereira D, Jamieson B, Rosiak C, Bales B, Kirchhoefer P, Youngberg S, McClanahan R, Fernandes P 2014. Human metabolism of solithromycin. In New antibacterial discovery and development, p 29. Gordon Res Conf New Antibact Discov Dev, Ventura, CA."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200215666140605130935"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01429-10"},{"key":"e_1_3_3_14_2","volume-title":"Safety testing of drug metabolites: guidance for industry","author":"FDA","year":"2016","unstructured":"FDA. 2016. Safety testing of drug metabolites: guidance for industry. FDA, Washington, DC. https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM079266.pdf."},{"key":"e_1_3_3_15_2","volume-title":"ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals","author":"European Medicines Agency","year":"2009","unstructured":"European Medicines Agency. 2009. ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals. European Medicines Agency, London, United Kingdom. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500002720.pdf."},{"key":"e_1_3_3_16_2","unstructured":"Pereira DP Degenhardt T Fernandes P. 2010. Comparison of CEM-101 metabolism in mice rats monkeys and humans abstr A-687. Abstr 50th Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology Washington DC."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04652-14"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01474-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01474-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:12:17Z","timestamp":1645477937000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01474-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1128\/AAC.01474-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01474-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"2017-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01474-17"}}