{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T02:03:56Z","timestamp":1770689036010,"version":"3.49.0"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Solithromycin, a new macrolide and the first fluoroketolide, is in late-stage clinical development and, like older macrolides, is primarily metabolized and excreted through liver-dependent mechanisms. This study evaluated the safety and pharmacokinetics of solithromycin in patients with chronic liver disease. This open-label, multiple-dose study in subjects with hepatic impairment and in healthy control subjects (matched for age, weight, and sex) enrolled 8 Child-Pugh class A (mild), 8 class B (moderate), and 8 class C (severe) patients and 9 healthy controls. Subjects (\n            <jats:italic>n<\/jats:italic>\n            = 33) received one 800-mg dose on day 1 followed by once-daily doses of 400 mg on days 2 through 5. The most commonly reported adverse events were mild diarrhea and mild headache, and no significant differences were noted between hepatically impaired subjects and healthy controls. The pharmacokinetics of plasma solithromycin in subjects with mild and moderate impairment was similar to that in control subjects. In subjects with severe impairment, total exposure to solithromycin at steady state (area under the plasma concentration-time curve [AUC\n            <jats:sub>0\u2013tau<\/jats:sub>\n            ]) was decreased compared to that in control subjects, which may have been related to the higher body mass index of individuals in this group. No greater accumulation was noted in any hepatically impaired cohort on day 5 compared to that in control subjects. No decrease in dosage is therefore needed when administering solithromycin to patients with mild, moderate, or severe hepatic impairment. Solithromycin was well tolerated in this patient population, and no significant differences in safety, compared to healthy controls, were noted.\n          <\/jats:p>","DOI":"10.1128\/aac.04652-14","type":"journal-article","created":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T02:22:21Z","timestamp":1428978141000},"page":"4379-4386","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Safety and Pharmacokinetics of Solithromycin in Subjects with Hepatic Impairment"],"prefix":"10.1128","volume":"59","author":[{"given":"Brian D.","family":"Jamieson","sequence":"first","affiliation":[{"name":"Cempra, Inc., Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Ciric","sequence":"additional","affiliation":[{"name":"Celerion, Montreal, Quebec, Canada"}],"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"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.01.026"},{"key":"e_1_3_3_3_2","volume-title":"Abstr 19th Eur Congr Clin Microbiol Infect Dis","author":"Jones RN","year":"2009","unstructured":"Jones RN, Sader HS, Biedenbach DJ. 2009. Antimicrobial characterization of CEM-101: activity against staphylococci, beta-haemolytic and viridans group streptococci, abstr P-1100. Abstr 19th Eur Congr Clin Microbiol Infect Dis."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01123-09"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00090-09"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00036-12"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00564-13"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01343-09"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00197-13"},{"key":"e_1_3_3_10_2","volume-title":"STI & AIDS World Congress","author":"Hook EW","year":"2013","unstructured":"Hook EW, Jamieson B, Oldach D, Harbison H, Whittington A, Fernandes P. 2013. A phase II dose ranging study to evaluate the efficacy and safety of single-dose oral solithromycin (CEM-101) for treatment of patients with uncomplicated urogenital gonorrhea, abstr O02.5. STI & AIDS World Congress, Vienna, Austria."},{"key":"e_1_3_3_11_2","volume-title":"Abstr Am Thorac Soc Int Conf","author":"Oldach DW","year":"2015","unstructured":"Oldach DW, Barrera CM, Metev H, Dvoretskiy LI, Mykietuk A, Mitha I, DeSalvo MC, Tanaseanu CM, Szabo P, Clark K, Jamieson B, Das A, Keedy K, Fernandes P. 2015. Oral solithromycin versus oral moxifloxacin for treatment of adult community-acquired bacterial pneumonia (CABP): results of the global phase-3 trial SOLITAIRE-ORAL, abstr 69069. Abstr Am Thorac Soc Int Conf."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01429-10"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1993.tb04692.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/31.suppl_E.57"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(03)00128-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.04.005"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.02.038"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.12.005"},{"key":"e_1_3_3_19_2","first-page":"851","volume-title":"The use of antibiotics: a comprehensive review with clinical emphasis","author":"Kucers A","year":"1987","unstructured":"Kucers A, Bennett N. 1987. Erythromycin, p 851\u2013882. In William Heinemann (ed), The use of antibiotics: a comprehensive review with clinical emphasis, 4th ed. William Heinemann Medical Books Ltd., London, United Kingdom.","edition":"4"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04568-14"},{"key":"e_1_3_3_21_2","volume-title":"Abstr 50th Intersci Conf Antimicrob Agents Chemother","author":"Andes DR","year":"2010","unstructured":"Andes DR, Okusanya OO, Forrest A, Bhavnani SM, Fernandes P, Ambrose PG. 2010. Pharmacokinetic-pharmacodynamic analysis of solithromycin (CEM-101) against Streptococcus pneumoniae using data from a murine-lung infection model, abstr A1-688. Abstr 50th Intersci Conf Antimicrob Agents Chemother."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00766-12"},{"key":"e_1_3_3_23_2","volume-title":"Abstr 50th Intersci Conf Antimicrob Agents Chemother","author":"Pereira DE","year":"2010","unstructured":"Pereira DE, Degenhardt T, Fernandes P. 2010. Comparison of CEM-101 metabolism in mice, rats, monkeys and humans, abstr A1-687. Abstr 50th Intersci Conf Antimicrob Agents Chemother."},{"key":"e_1_3_3_24_2","volume-title":"Pharmacokinetics in patients with impaired hepatic function\u2014study design, data analysis, and impact on dosing and labeling","author":"Department of Health and Human Services","year":"2003","unstructured":"Department of Health and Human Services. 2003. Pharmacokinetics in patients with impaired hepatic function\u2014study design, data analysis, and impact on dosing and labeling. HHS, Washington, DC. http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm072123.pdf."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04652-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04652-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:05:37Z","timestamp":1645484737000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04652-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1128\/AAC.04652-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04652-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8]]},"assertion":[{"value":"2014-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}