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Pharmacokinetics of Gepotidacin in Subjects With Normal Hepatic Function and Hepatic Impairment
- Source :
- Clinical Pharmacology in Drug Development
- Publication Year :
- 2021
- Publisher :
- John Wiley and Sons Inc., 2021.
-
Abstract
- Gepotidacin is a novel triazaacenaphthylene bacterial topoisomerase inhibitor. This phase 1 nonrandomized, open‐label, multicenter, 2‐part study evaluated the pharmacokinetics, safety, and tolerability of oral gepotidacin 1500 mg in 3 different hepatic settings (normal, moderate impairment, and severe impairment). Gepotidacin was safe and generally tolerated in all subjects. Compared to subjects with normal hepatic function, gepotidacin plasma area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) and maximum concentration significantly increased by 1.7‐ and 1.9‐fold, respectively, in severe hepatic impairment; increases in moderate impairment were not statistically significant. No significant effect was observed for gepotidacin plasma elimination half‐life (geometric mean range, 8.2–9.1 hours) across hepatic groups. Renal clearance increased in moderate (16%) and severe (52%) hepatic impairment vs normal. The mean fraction of gepotidacin dose excreted in urine increased with increasing hepatic impairment (normal, 7.5%; moderate, 11.2%; and severe, 19.9%). Urine gepotidacin concentrations remained high for 12 hours in all hepatic groups after dosing. Saliva gepotidacin concentrations displayed a linear relationship with plasma concentrations (R2 = 0.76). The ratio of saliva AUC to unbound plasma AUC and elimination half‐life were not affected by hepatic impairment. These data indicate that gepotidacin dose adjustment is not required in mild to moderate hepatic impairment; severe hepatic impairment may require increases in dosing interval or dose reduction.
- Subjects :
- safety
Adult
Male
Gepotidacin
medicine.medical_specialty
Saliva
Adolescent
gepotidacin
Pharmaceutical Science
Original Manuscript
Urine
030226 pharmacology & pharmacy
Gastroenterology
Severity of Illness Index
Hepatic function
03 medical and health sciences
Young Adult
0302 clinical medicine
Pharmacokinetics
Internal medicine
Medicine
Humans
Pharmacology (medical)
Dosing
Aged
Aged, 80 and over
business.industry
Acenaphthenes
Hepatic impairment
Liver Diseases
liver failure
Articles
Middle Aged
Anti-Bacterial Agents
Tolerability
030220 oncology & carcinogenesis
Area Under Curve
Female
business
pharmacokinetics
Heterocyclic Compounds, 3-Ring
Half-Life
Subjects
Details
- Language :
- English
- ISSN :
- 21607648 and 2160763X
- Volume :
- 10
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Clinical Pharmacology in Drug Development
- Accession number :
- edsair.doi.dedup.....2ac5ecb5c65843d2c88cde6dd1a879e0