Pharmacokinetic, tissue distribution, permeability, protein binding and stability studies of finerenone in SD rats using validated UPLC and LC-MS method.

Finerenone (FNR) is a novel selective nonsteroidal mineralocorticoid receptor antagonist for the treatment of chronic kidney disease associated with diabetes. We aimed to develop a novel, reproducible and highly sensitive bioanalytical method in liquid chromatography coupled with mass spectrometry (LC-MS/MS) for FNR was validate in rat plasma for the first time and determining their pharmacokinetic (PK) and tissue distribution (TD) in SD rats. We have performed the in-vivo PK, TD and in-vitro solubility, Fasted/Feeded simulated intestinal (FaSSIF) and gastric fluid (FaSSGF) stability, plasma stability, microsomal stability, plasma protein binding (PPB), blood plasma partitioning, parallel artificial membrane permeability assay (PAMPA) and in-situ single pass intestinal permeability (SPIP) for FNR. FNR was more soluble in intestinal fluid and stable in FaSSIF, FeSSIF than FaSSGF. FNR was stable in plasma (91.98%) and metabolized in rat liver microsome (90.30%) at 5 μM concentration up to 3 and 1 h, respectively. PPB was found 94.11% and 96.97% at 5 and 10 μM concentration, respectively. The plasma partition coefficient results of FNR were found the fast equilibrium between blood and plasma. PAMPA and SPIP results demonstrate the passive permeability of FNR was high. Oral and intravenous (IV) administration of FNR, absolute bioavailability was observed 49.17%. The distribution of FNR was found the maximum concentration in following order: intestine> kidney> lungs> spleen> muscle> heart> brain> pancreas> liver. The all above in-vitro as well as in-vivo study are support the preclinical and clinical application of FNR.