{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:02:26Z","timestamp":1753182146832},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gepotidacin is a novel, bactericidal, first\u2010in\u2010class triazaacenaphthylene antibiotic in late\u2010phase development for uncomplicated urinary tract infection and uncomplicated urogenital gonorrhea. Two clinical studies were conducted to assess the pharmacokinetics (PK) and interethnic comparisons of oral gepotidacin (free\u2010base and to\u2010be\u2010marketed mesylate formulations) administered as single doses ranging from 1500 to 3000\u00a0mg in fed and fasted states, and as 2\u00a0\u00d7\u00a03000\u2010mg doses given 12\u00a0hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration\u2010time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non\u2010Japanese participant data showed slightly higher plasma maximum concentration (7%\u201030%) yet similar plasma AUCs; slightly lower urine AUCs (11%\u201018%) were observed. The slightly higher plasma exposures in healthy Japanese versus White participants in the same study were attributed to lower mean body weights (64\u00a0kg versus \u224880\u00a0kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety\u2010risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies.<\/jats:p>","DOI":"10.1002\/cpdd.1192","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T12:10:01Z","timestamp":1670242201000},"page":"38-56","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants"],"prefix":"10.1002","volume":"12","author":[{"given":"Aline","family":"Barth","sequence":"first","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"},{"name":"Present affiliation: Global Blood Therapeutics  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Hossain","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"},{"name":"Present affiliation: Servier Pharmaceuticals  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline R.","family":"Perry","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette S.","family":"Gross","sequence":"additional","affiliation":[{"name":"GSK R&amp;D  Sydney AU"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Ogura","sequence":"additional","affiliation":[{"name":"GSK  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaila","family":"Shabbir","sequence":"additional","affiliation":[{"name":"GSK  Stevenage UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebin","family":"Thomas","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne F.","family":"Dumont","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"},{"name":"Present affiliation: Boston Pharmaceuticals  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darin B.","family":"Brimhall","sequence":"additional","affiliation":[{"name":"PPD  Las Vegas Nevada USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meenakshi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Swift","sequence":"additional","affiliation":[{"name":"GSK  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02820-15"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00315"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"issue":"7","key":"e_1_2_9_5_1","first-page":"e00199","article-title":"Phase 2a pharmacokinetic, safety, and exploratory efficacy evaluation of oral gepotidacin (GSK2140944) in female participants with uncomplicated urinary tract infection (acute uncomplicated cystitis)","author":"Overcash JS","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_9_6_1","unstructured":"MushtaqS VickersA SadoukiZ et\u00a0al.In vitro activities of gepotidacin a novel triazaacenaphthylene topoisomerase IV and DNA gyrase inhibitor against gram\u2010negative bacteria andStaphylococcus saprophyticus[poster P1849]. Presented at: the 29th European Congress of Clinical Microbiology & Infectious Diseases; April 13\u201316 2019;Amsterdam The Netherlands."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky162"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02047-16"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02095-16"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy145"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01221-18"},{"key":"e_1_2_9_12_1","unstructured":"ClinicalTrials.gov.2019.NCT04010539: a study evaluating efficacy and safety of gepotidacin compared with ceftriaxone plus azithromycin in the treatment of uncomplicated urogenital gonorrhea.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04010539. 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