Mass balance and biotransformation of finerenone, a nonsteroidal 
mineralocorticoid receptor antagonist, were investigated in four healthy male 
volunteers following a single oral administration of 10 mg (78 μCi) of 
[14C]finerenone and compared with data from studies in dogs and rats. The total 
recovery of the administered radioactivity was 101% in humans, 94.7% in dogs, 
and 95.2% in rats. In humans, radioactivity was mainly excreted renally (80%); 
in rats, it was primarily the biliary/fecal route (76%); and in dogs, excretion 
was more balanced. Finerenone was extensively metabolized in all species by 
oxidative biotransformation, with minor amounts of unchanged drug in excreta 
(humans: 1%; dogs, rats: <9%). In vitro studies suggested cytochrome P450 3A4 
was the predominant enzyme involved in finerenone metabolism in humans. Primary 
metabolic transformation involved aromatization of the dihydronaphthyridine 
moiety of metabolite M1 as a major clearance pathway with a second oxidative 
pathway leading to M4. These were both prone to further oxidative 
biotransformation reactions. Naphthyridine metabolites (M1-M3) were the dominant 
metabolites identified in human plasma, with no on-target pharmacological 
activity. In dog plasma, finerenone and metabolite M2 constituted the major 
components; finerenone accounted almost exclusively for drug-related material in 
rat plasma. For metabolites M1-M3, axial chirality was observed, represented by 
two atropisomers (e.g., M1a and M1b). Analysis of plasma and excreta showed one 
atropisomer (a-series, >79%) of each metabolite predominated in all three 
species. In summary, the present study demonstrates that finerenone is cleared 
by oxidative biotransformation, mainly via naphthyridine derivatives.