BACKGROUND AND OBJECTIVES: Finerenone is a selective, non-steroidal 
mineralocorticoid receptor antagonist. In vivo and in vitro studies were 
performed to assess absolute bioavailability of finerenone, the effect of 
metabolic enzyme inhibitors on the pharmacokinetics of finerenone and its 
metabolites, the quantitative contribution of the involved enzymes cytochrome 
P450 (CYP) 3A4 and CYP2C8 and the relevance of gut wall versus liver metabolism.
METHODS: The pharmacokinetics, safety and tolerability of finerenone (1.25-10 mg 
orally or 0.25-1.0 mg intravenously) were evaluated in healthy male volunteers 
in four crossover studies. Absolute bioavailability was assessed in volunteers 
receiving finerenone orally and by intravenous infusion (n = 15) and the effects 
of erythromycin (n = 15), verapamil (n = 13) and gemfibrozil (n = 16) on 
finerenone pharmacokinetics were investigated. Finerenone was also incubated 
with cryopreserved human hepatocytes in vitro in the presence of erythromycin, 
verapamil or gemfibrozil.
RESULTS: Finerenone absolute bioavailability was 43.5% due to first-pass 
metabolism in the gut wall and liver. The geometric mean AUC0-∞ ratios of 
finerenone (drug + inhibitor/drug alone) were 3.48, 2.70 and 1.10 with 
erythromycin, verapamil and gemfibrozil, respectively. The contribution ratio of 
CYP3A4 to the metabolic clearance of finerenone derived from these values was 
0.88-0.89 and was consistent with estimations based on in vitro data, with the 
remaining metabolic clearance due to CYP2C8 involvement.
CONCLUSION: Finerenone is predominantly metabolized by CYP3A4 in the gut wall 
and liver. Increases in systemic exposure upon concomitant administration of 
inhibitors of this isoenzyme are predictable and consistent with in vitro data. 
Inhibition of CYP2C8, the second involved metabolic enzyme, has no relevant 
effect on finerenone in vivo.