1. Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants.
- Author
-
Barth A, Hossain M, Perry CR, Gross AS, Ogura H, Shabbir S, Thomas S, Dumont EF, Brimhall DB, Srinivasan M, and Swift B
- Subjects
- Humans, Healthy Volunteers, Anti-Bacterial Agents pharmacokinetics, Acenaphthenes pharmacokinetics, Heterocyclic Compounds, 3-Ring pharmacokinetics
- Abstract
Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic in late-phase 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-base and to-be-marketed mesylate formulations) administered as single doses ranging from 1500 to 3000 mg in fed and fasted states, and as 2 × 3000-mg doses given 12 hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration-time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non-Japanese participant data showed slightly higher plasma maximum concentration (7%-30%) yet similar plasma AUCs; slightly lower urine AUCs (11%-18%) 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 kg versus ≈80 kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety-risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies., (© 2022 GSK. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
- Published
- 2023
- Full Text
- View/download PDF