Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals with Mild or Moderate Hepatic Impairment

• Published in: European journal of drug metabolism and pharmacokinetics 2019-10, Vol.44 (5), p.619-628
• Main Authors: Heinig, Roland, Lambelet, Marc, Nagelschmitz, Johannes, Alatrach, Abir, Halabi, Atef
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Female; Half-Life; Human Physiology; Humans; Liver - metabolism; Liver Diseases - metabolism; Male; Medical Biochemistry; Middle Aged; Mineralocorticoid Receptor Antagonists - pharmacokinetics; Naphthyridines - pharmacokinetics; Original Research Article; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-019-00547-x

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 ( C max ) was unchanged. No clear effects on AUC or C max 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 C max , a dose adaptation does not appear to be warranted in patients with mild or moderate hepatic impairment.