دورية أكاديمية
Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects.
| العنوان: | Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects. |
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| المؤلفون: | Tiffany C; GSK, Collegeville, Pennsylvania, USA., Dumont EF; GSK, Collegeville, Pennsylvania, USA., Hossain M; GSK, Collegeville, Pennsylvania, USA., Srinivasan M; GSK, Collegeville, Pennsylvania, USA., Swift B; GSK, Research Triangle Park, North Carolina, USA. |
| المصدر: | Clinical and translational science [Clin Transl Sci] 2022 Sep; Vol. 15 (9), pp. 2251-2264. Date of Electronic Publication: 2022 Jul 13. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Malden, MA : WileyBlackwell Pub., 2008- |
| مواضيع طبية MeSH: | Single-Blind Method*, Acenaphthenes ; Administration, Oral ; Adult ; Aged ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Double-Blind Method ; Healthy Volunteers ; Heterocyclic Compounds, 3-Ring ; Humans |
| مستخلص: | Gepotidacin, a novel, first-in-class triazaacenaphthylene antibiotic, inhibits bacterial DNA replication by a distinct mechanism of action. We report the pharmacokinetics (PKs), safety, and tolerability of gepotidacin following single or multiple ascending doses. Studies 1 and 2 were randomized, single-blind, placebo-controlled trials in healthy adults aged 18-60 years, who received single (study 1 [NCT02202187]; 100-3000 mg) or repeat (study 2 [NCT01706315]; 400 mg twice daily to 2000 mg thrice daily) ascending doses of gepotidacin. Study 3 (NCT02045849) was an open-label, three-part, study in healthy adults; here, we report on part 3, a two-period, repeat-dose, crossover study. Healthy elderly participants received repeat 1500 mg gepotidacin twice daily with or without a moderate-fat meal. Primary end points were PKs (studies 1 and 2) and safety (studies 1 and 3 part 3). Gepotidacin PK parameters were comparable across all ages and were dose proportional. In all studies, gepotidacin was readily absorbed with median time to maximum concentration observed ranging from 1.0 to 4.0 h across all doses. Median apparent terminal phase half-life was consistent across studies and doses (range: 5.97-19.2 h). Steady-state was achieved following repeated dosing for 3-5 days; gepotidacin PK parameters were time invariant after repeated oral dosing. A moderate-fat meal did not affect gepotidacin PK parameters. Gepotidacin was generally well-tolerated, with no drug-related serious adverse events reported. Collectively, these PK and safety data across a wide range of doses in healthy participants aged greater than or equal to 18 years support the development of gepotidacin in further clinical studies. (© 2022 GSK. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.) |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT02202187; NCT01706315; NCT02045849 |
| المشرفين على المادة: | 0 (Acenaphthenes) 0 (Heterocyclic Compounds, 3-Ring) DVF0PR037D (gepotidacin) |
| تواريخ الأحداث: | Date Created: 20220630 Date Completed: 20220914 Latest Revision: 20230124 |
| رمز التحديث: | 20230126 |
| مُعرف محوري في PubMed: | PMC9468557 |
| DOI: | 10.1111/cts.13359 |
| PMID: | 35769034 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1752-8062 |
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| DOI: | 10.1111/cts.13359 |