Abstract
Background and Objectives
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
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
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 (Cmax) was unchanged. No clear effects on AUC or Cmax were seen in participants with mild hepatic impairment. Finerenone was safe and well tolerated in all participants.
Conclusion
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 Cmax, a dose adaptation does not appear to be warranted in patients with mild or moderate hepatic impairment.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
Dr. Gabriele Rohde of Bayer AG (Wuppertal, Germany) was responsible for bioanalyses. Editorial assistance, funded by Bayer AG, was provided by Oxford PharmaGenesis Ltd, Oxford, UK.
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Funding
This research was funded by the sponsor, Bayer AG. Bayer AG agreed to the publication of the present data.
Conflict of interest
RH and JN are employees of Bayer AG. ML is an employee of CHRESTOS Concept GmbH & Co. KG, which received funding for this analysis from Bayer AG. AA and AH are employees of CRS Clinical Research Services Kiel GmbH, which received funding for study conduct from Bayer AG. In addition, RH and JN have stock in Bayer AG, but are not paid in stock or stock options.
Ethical approval
The study protocol (no. 14510) was reviewed and approved by the Independent Ethics Committee of the Medical Council of Schleswig–Holstein (Bad Segeberg, Germany). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all participants before study commencement.
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Heinig, R., Lambelet, M., Nagelschmitz, J. et al. Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals with Mild or Moderate Hepatic Impairment. Eur J Drug Metab Pharmacokinet 44, 619–628 (2019). https://doi.org/10.1007/s13318-019-00547-x
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DOI: https://doi.org/10.1007/s13318-019-00547-x