{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:18:10Z","timestamp":1768349890668,"version":"3.49.0"},"reference-count":12,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"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":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Omadacycline, a first-in-class aminomethylcycline antibiotic, is related to tetracyclines but is structurally modified to circumvent mechanisms of resistance to tetracyclines. Omadacycline demonstrates potent activity against a broad range of pathogens, including drug-resistant strains, and is in late-stage development for treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Previous studies support an intravenous-to-oral transition regimen with 300-mg once-daily oral dosing. This phase 1 study investigated the pharmacokinetics and safety\/tolerability of multiple oral omadacycline doses higher than 300 mg. Using a 3-period crossover design, healthy adults were randomized to receive oral omadacycline at 300, 450, and 600 mg in variable sequence (\n            <jats:italic>n<\/jats:italic>\n            = 26) or placebo (\n            <jats:italic>n<\/jats:italic>\n            = 7) once daily for 5 consecutive days per period. In plasma, omadacycline maximum concentration and total exposure increased with increasing dose but were less than dose proportional. The kinetics of omadacycline plasma accumulation were similar between dose levels; exposure on day 5 was \u223c50% higher than that on day 1. Omadacycline plasma concentrations on day 1 of 450-mg dosing were similar to those on day 5 of 300-mg dosing. All doses were generally well tolerated, but the 600-mg dose was associated with more gastrointestinal adverse events.\n          <\/jats:p>","DOI":"10.1128\/aac.01487-17","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T16:30:32Z","timestamp":1511800232000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Safety and Pharmacokinetics of the Aminomethylcycline Antibiotic Omadacycline Administered to Healthy Subjects in Oral Multiple-Dose Regimens"],"prefix":"10.1128","volume":"62","author":[{"given":"Lu Ann","family":"Bundrant","sequence":"first","affiliation":[{"name":"PPD Phase I Clinic, Austin, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Tzanis","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne","family":"Garrity-Ryan","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Bai","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surya","family":"Chitra","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Manley","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Villano","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0100"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.07.029"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.2.232-260.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01066-13"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01536-15"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01242-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00774-16"},{"key":"e_1_3_2_9_2","unstructured":"O'Riordan WA Green S Overcash JS Pulijiz I Metallidis S Gardovskis J Garrity-Ryan L Das A Tzanis E Eckburg P Manley A Villano S Loh E. 2017. A phase 3 randomized double-blind multi-center study to compare the safety and efficacy of oral and IV omadacycline to linezolid for treating adult subjects with ABSSSI (the OASIS study) abstr 630. Abstr 27th Eur Congr Clin Microbiol Infect Dis (ECCMID) Vienna Austria."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"Stets R Popescu M Gonong J Mitha I Nseir W Madej A Kirsch C Das A Garrity-Ryan L Steenbergen J Manley A Eckburg P Villano S Tzanis E McGovern P Loh E. 2017. A phase 3 randomized double-blind multi-center study to compare the safety and efficacy of IV to oral omadacycline to moxifloxacin for the treatment of adult subjects with CABP (The OPTIC Study). IDWeek 2017 abstr 1883.","DOI":"10.1093\/ofid\/ofx163.1413"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.814"},{"key":"e_1_3_2_12_2","volume-title":"ICH harmonised tripartite guideline\u2014guideline for good clinical practice: E6(R1)","author":"ICH Expert Working Group","year":"1996","unstructured":"ICH Expert Working Group. 1996. ICH harmonised tripartite guideline\u2014guideline for good clinical practice: E6(R1). International Council for Harmonisation (ICH), Geneva, Switzerland. https:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E6\/E6_R1_Guideline.pdf."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026451721686"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01487-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01487-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:10:07Z","timestamp":1645477807000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01487-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1128\/AAC.01487-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01487-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2]]},"assertion":[{"value":"2017-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01487-17"}}