{"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":1784417128825,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Zoliflodacin is a first\u2010in\u2010class oral spiropyrimidinetrione antibiotic being developed for patients with uncomplicated gonorrhea, including those infected with multidrug\u2010resistant strains. Because zoliflodacin is metabolized by cytochrome P450 3A4 (CYP3A4), concomitant administration with a CYP3A inhibitor has the potential to increase zoliflodacin plasma exposure. The aim of this phase 1 drug\u2013drug interaction (DDI) study was to assess the effect of the strong CYP3A4 inhibitor itraconazole on the pharmacokinetics (PK) and safety of a 3\u2009g single oral dose of zoliflodacin. This was an open label, 2\u2010period, 2\u2010treatment, fixed sequence crossover DDI study. Eighteen eligible adult participants were dosed and completed the study. When zoliflodacin was co\u2010administered with itraconazole at steady state, as determined by itraconazole trough plasma concentrations, zoliflodacin exposure increased as measured by peak concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) by 1.03\u2010fold and by area under the plasma\u2010concentration time curve (AUC) from time 0 to last measurable plasma concentration (AUC\n                    <jats:sub>0\u2010last<\/jats:sub>\n                    ) and from time 0 extrapolated to infinity (AUC\n                    <jats:sub>0\u2010\u221e<\/jats:sub>\n                    ) by 1.39\u2010 and 1.38\u2010fold, respectively. Eight participants (44.4%) had a total of 15 mild treatment\u2010emergent adverse events (TEAEs), with three considered related to treatment. There were no deaths or serious TEAEs and no participant withdrew. No clinically significant abnormal laboratory values, vital signs, or electrocardiogram findings were reported. In conclusion, the C\n                    <jats:sub>max<\/jats:sub>\n                    of zoliflodacin was essentially unchanged (1.03\u2010fold higher) when co\u2010administered with a strong CYP3A4 inhibitor, while AUC exposures increased by less than 1.5\u2010fold, which, combined with an acceptable safety profile, indicate a low DDI potential between zoliflodacin and CYP3A4 inhibitors.\n                  <\/jats:p>","DOI":"10.1111\/cts.70515","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:05:04Z","timestamp":1772967904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Drug\u2013Drug Interaction Potential Between the Oral Antibiotic Zoliflodacin and the\n                    <scp>CYP3A4<\/scp>\n                    Inhibitor Itraconazole: A Phase 1 Study in Healthy Participants"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8914","authenticated-orcid":false,"given":"Alison","family":"Luckey","sequence":"first","affiliation":[{"name":"Global Antibiotic Research &amp; Development Partnership (GARDP)  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajal B.","family":"Larson","sequence":"additional","affiliation":[{"name":"Innoviva Specialty Therapeutics, Inc.  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