Pharmacokinetics of Gepotidacin in Renal Impairment

Mohammad Hossain, Courtney Tiffany, Aparna Raychaudhuri, Dung Nguyen, Guoying Tai, Harry Alcorn, Richard A. Preston, Thomas Marbury, Etienne Dumont

Research output: Contribution to journalArticle

Abstract

Gepotidacin is a novel triazaacenaphthylene bacterial topoisomerase inhibitor. In this phase 1, nonrandomized, open-label, parallel-group, multicenter, multipart study, the pharmacokinetics, safety, and tolerability of a single intravenous (IV) dose of gepotidacin 750 mg over 2 hours were evaluated in subjects with normal renal function, in those with moderate and severe renal impairment, and in end-stage renal disease (ESRD) on and not on dialysis. Administration of IV gepotidacin 750 mg was safe and generally tolerated in the study subjects. Dosing in severe renal impairment with and without hemodialysis resulted in significant increases in plasma drug levels and decreases in clearance. The geometric mean elimination half-life (t½) was minimally impacted (range 9.45 to 11.5 hours) in all the renal-impairment groups relative to normal renal function. Regardless of renal function, urine gepotidacin concentrations remained considerably high over a 12-hour period. Saliva concentrations displayed a linear relationship with plasma concentrations. The t½ in saliva was not impacted in the moderate-impairment and ESRD subjects and was comparable to t½ in plasma. Over a 4-hour dialysis, approximately 6% of the gepotidacin dose was removed. Overall, subjects with severe renal impairment and ESRD with and without hemodialysis may require adjustment in dose or dosing frequency.

Original languageEnglish (US)
Pages (from-to)560-572
Number of pages13
JournalClinical Pharmacology in Drug Development
Volume9
Issue number5
DOIs
StatePublished - Jul 1 2020

Keywords

  • end-stage renal disease
  • gepotidacin
  • pharmacokinetics
  • physiologically based pharmacokinetic modeling
  • renal impairment
  • safety

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology (medical)

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  • Cite this

    Hossain, M., Tiffany, C., Raychaudhuri, A., Nguyen, D., Tai, G., Alcorn, H., Preston, R. A., Marbury, T., & Dumont, E. (2020). Pharmacokinetics of Gepotidacin in Renal Impairment. Clinical Pharmacology in Drug Development, 9(5), 560-572. https://doi.org/10.1002/cpdd.807