Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals with Mild or Moderate Hepatic Impairment.
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
pubmed:
3
3
2019
medline:
6
2
2020
entrez:
3
3
2019
Statut:
ppublish
Résumé
Finerenone (BAY 94-8862) is a selective, nonsteroidal mineralocorticoid receptor antagonist. The aim of this study was to assess the effect of mild or moderate hepatic impairment on the pharmacokinetics, safety and tolerability of finerenone. The study was conducted in a single-center, nonrandomized, noncontrolled, nonblinded observational design with group stratification. A single oral 5-mg dose of finerenone was administered as a tablet to participants with mild or moderate hepatic impairment (Child-Pugh A, score 5-6 [n = 9], or Child-Pugh B, score 7-9 [n = 9], respectively) and to age-, weight- and sex-matched healthy participants (n = 9). The pharmacokinetics of finerenone and its metabolites were assessed in plasma and urine, and safety and tolerability were monitored. Finerenone area under the plasma concentration-time curve (AUC) and unbound AUC were 38% and 55% greater, respectively, in participants with moderate hepatic impairment than in healthy participants, whereas maximum plasma concentration (C The effects of mild or moderate hepatic impairment on systemic exposure of finerenone are small, consistent with its low hepatic extraction and preponderance of gastrointestinal over hepatic first-pass clearance. Considering the small increases in AUC and the absence of changes in C
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Finerenone (BAY 94-8862) is a selective, nonsteroidal mineralocorticoid receptor antagonist. The aim of this study was to assess the effect of mild or moderate hepatic impairment on the pharmacokinetics, safety and tolerability of finerenone.
METHODS
METHODS
The study was conducted in a single-center, nonrandomized, noncontrolled, nonblinded observational design with group stratification. A single oral 5-mg dose of finerenone was administered as a tablet to participants with mild or moderate hepatic impairment (Child-Pugh A, score 5-6 [n = 9], or Child-Pugh B, score 7-9 [n = 9], respectively) and to age-, weight- and sex-matched healthy participants (n = 9). The pharmacokinetics of finerenone and its metabolites were assessed in plasma and urine, and safety and tolerability were monitored.
RESULTS
RESULTS
Finerenone area under the plasma concentration-time curve (AUC) and unbound AUC were 38% and 55% greater, respectively, in participants with moderate hepatic impairment than in healthy participants, whereas maximum plasma concentration (C
CONCLUSION
CONCLUSIONS
The effects of mild or moderate hepatic impairment on systemic exposure of finerenone are small, consistent with its low hepatic extraction and preponderance of gastrointestinal over hepatic first-pass clearance. Considering the small increases in AUC and the absence of changes in C
Identifiants
pubmed: 30825073
doi: 10.1007/s13318-019-00547-x
pii: 10.1007/s13318-019-00547-x
doi:
Substances chimiques
Mineralocorticoid Receptor Antagonists
0
Naphthyridines
0
finerenone
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
619-628Références
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