{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T23:25:28Z","timestamp":1784417128996,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gonorrhea is a sexually transmitted infection for which antibiotic treatment options have declined due to increasing antibiotic resistance. Zoliflodacin, an investigational oral spiropyrimidinetrione antibiotic with activity against <jats:italic>Neisseria gonorrhoeae<\/jats:italic> strains that are multidrug\u2010resistant, including to third\u2010generation cephalosporins, is in phase III development for uncomplicated gonorrhea. This phase I, parallel, open\u2010label, randomized, crossover study in healthy adults evaluated the effect of food on the pharmacokinetics of single 3 or 4\u00a0g doses of zoliflodacin administered as granules for oral suspension in the fasted state or after consumption of a standardized high\u2010fat meal. Forty\u2010seven out of 48 randomized subjects completed the study. Oral administration of zoliflodacin with food delayed the absorption rate, compared with fasted state, with time to maximum concentration (<jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>) increasing from 3 to 6\u00a0h for the 3\u00a0g dose, and 2.5 to 4\u00a0h for the 4\u00a0g dose, but had no impact on the elimination of zoliflodacin. The maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2010time curve from time 0 to 24\u2009h (AUC<jats:sub>(0\u201324)<\/jats:sub>) significantly increased with food by 52% and 94% for the 3\u00a0g dose, and by 89% and 108% for the 4\u00a0g dose. Forty\u2010two percent of participants reported a total of 34 treatment\u2010emergent adverse events (TEAEs), which were all considered mild in severity. Headache was the most common TEAE (22\/48 subjects, 45.8%) and the only TEAE reported in more than one subject. In conclusion, administration of single 3 and 4\u00a0g doses of zoliflodacin as granules for oral suspension, with a high\u2010fat meal was well\u2010tolerated and resulted in statistically significant increases in peak and overall systemic exposure to zoliflodacin.<\/jats:p>","DOI":"10.1111\/cts.13487","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T06:52:25Z","timestamp":1677221545000},"page":"770-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of food on the pharmacokinetics of zoliflodacin granules for oral suspension: Phase I <scp>open\u2010label<\/scp> randomized cross\u2010over study in healthy subjects"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8914","authenticated-orcid":false,"given":"Alison","family":"Luckey","sequence":"first","affiliation":[{"name":"GARDP  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-3991","authenticated-orcid":false,"given":"Emilie","family":"Alirol","sequence":"additional","affiliation":[{"name":"GARDP  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Delhomme","sequence":"additional","affiliation":[{"name":"DNDi  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Entasis Therapeutics  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Bettiol","sequence":"additional","affiliation":[{"name":"GARDP  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mueller","sequence":"additional","affiliation":[{"name":"Entasis Therapeutics  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seamus","family":"O'Brien","sequence":"additional","affiliation":[{"name":"GARDP  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Yves","family":"Gillon","sequence":"additional","affiliation":[{"name":"DNDi  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0128-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.18.228486"},{"key":"e_1_2_10_4_1","unstructured":"CDC.Antibiotic resistance threats in the United States.2019. 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