In Munich Wistar Frömter (MWF) rats, finerenone (BAY 94-8862) dramatically lowers systolic blood pressure (SBP) and reduces proteinuria by >40% [1].

Animal/Disease Models: 12weeks old MWF rats[1]
Doses: 10 mg/kg
Route of Administration: Po; one time/day for 4 weeks.
Experimental Results: The systolic blood pressure of MWF rats was Dramatically diminished; resulting in significant albuminuria in the MWF model. Dramatically diminished (>40%).

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Animal/Disease Models: 12weeks old MWF rats[1]
Doses: 10 mg/kg
Route of Administration: Po; one time/day for 4 weeks.
Experimental Results: The systolic blood pressure of MWF rats was Dramatically diminished; resulting in significant albuminuria in the MWF model. Dramatically diminished (>40%).

Absorption, Distribution and Excretion
A 10 mg oral dose of finerenone reaches a Cmax of 351 µg/L, with a Tmax of 1.5 hours, and an AUC of 2820 µg\*h/L in plasma. The same dose of finerenone reaches a Cmax of 226 µg/L, with a Tmax of 1.5 hours, and an AUC of 1840 µg\*h/L in whole blood. Regular doses of 20 mg of finerenone reach a geometric mean steady state Cmax of 160 µg/L with an AUC of 686 µg\*h/L.
The majority of the dose recovered in urine was in the form of the M2, M3 (47.8%), and M4 metabolites; <1.3% of the dose recovered in the urine was as the unchanged parent compound. The majority of the dose recovered in the feces was as the M5 metabolite, with only 0.2% eliminated as the unchanged parent compound. The M1 metabolite made up <1.5% of the recovered dose in urine and feces. Finerenone is not expected to be metabolized by the intestinal microflora.
The volume of distribution of finerenone as steady state is 52.6L.
The systemic clearance of finerenone is approximately 25 L/h.

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Metabolism / Metabolites
Finerenone is approximately 90% metabolized by CYP3A4, and 10% metabolized by CYP2C8. There is a minor contribution to metabolism by CYP1A1. Finerenone has no active metabolites. Finerenone is aromatized to the M1 metabolite by CYP3A4 and CYP2C8, which is further hydroxylated by CYP3A4 to the M2 metabolite, and finally oxidized bye CYP3A4 to the M3 metabolite. Alternatively, finerenone can undergo epoxidation and possibly hydrolysis by CYP3A4 and CYP2C8 to form the M4 metabolite, which is hydroxylated again by CYP3A4 to the M5 metabolite, and oxidized to the M8 metabolite. Finerenone can also be hydroxylated by CYP2C8 to the M7 metabolite, and further oxidized to the M9 metabolite. The M10 metabolite is formed by the demethylation, oxidation, and ring opening of finerenone. The M13 metabolite is formed through de-ethylation of finerenone by CYP1A1, and the M14 metabolite is formed through an undefined multi-step process involving CYP2C8 and CYP3A4.

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Biological Half-Life
The half life of a 10 mg dose of finerenone in 4 healthy men was 17.4 hours in plasma and 12.3 hours in whole blood. The terminal half life of finerenone is approximately 2-3 hours.

Hepatotoxicity
In placebo-controlled trials of finerenone in several thousand patients, there was usually no mention of serum enzyme elevations or hepatotoxicity. In the largest placebo controlled trial, the rate of “hepatobiliary” adverse events was similar in patients on finerenone compared to placebo (4.4% vs 4.8%), and there were no reported hepatic serious adverse events. Since its approval and more widespread use, finerenone has not been implicated in instances of acute hepatic injury and the product label does not mention aminotransferase elevations or clinically apparent liver injury in lists of potential adverse events.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of finerenone during breastfeeding. Finerenone is 92% bound to plasma proteins, so amounts in milk are likely to be low. However, the manufacturer recommends avoiding breastfeeding during treatment and for 1 day after treatment.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Finerenone is 92% protein bound in plasma; predominantly to serum albumin.

[1]. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7(8):1385-1403.

[2]. Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress. Front Pharmacol. 2018;9:1131. Published 2018 Oct 9.

Pharmacodynamics
Finerenone is a non-steroidal mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. It has a moderate duration of action as it is taken once daily, and a wide therapeutic window as patients were given doses from 1.25 mg to 80 mg in clinical trials. Patients should be counselled regarding the risk of hyperkalemia.

C21H22N4O3

378.4244

378.169

1050477-31-0

(Rac)-Finerenone;1050477-27-4

60150535

White to off-white solid powder

4.273

2

6

5

28

670

1

CCOC1=NC=C(C2=C1[C@@H](C(=C(N2)C)C(=O)N)C3=C(C=C(C=C3)C#N)OC)C

BTBHLEZXCOBLCY-QGZVFWFLSA-N

InChI=1S/C21H22N4O3/c1-5-28-21-18-17(14-7-6-13(9-22)8-15(14)27-4)16(20(23)26)12(3)25-19(18)11(2)10-24-21/h6-8,10,17,25H,5H2,1-4H3,(H2,23,26)/t17-/m1/s1

(4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~200 mg/mL (~528.51 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 1.93 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 19.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.93 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 19.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)