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%).

---

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
Following oral administration of 10 mg fenelazol, the peak plasma concentration (Cmax) was 351 µg/L, the time to peak concentration (Tmax) was 1.5 hours, and the AUC was 2820 µgh/L. The same dose of fenelazol resulted in a peak plasma concentration (Cmax) of 226 µg/L in whole blood, a time to peak concentration (Tmax) of 1.5 hours, and an AUC of 1840 µgh/L. The steady-state geometric mean peak plasma concentration (Cmax) of a standard dose of 20 mg fenelazol was 160 µg/L, and the AUC was 686 µgh/L. Most of the drug recovered in urine was in the form of M2, M3 (47.8%), and M4 metabolites; less than 1.3% of the recovered drug was unmetabolized parent compound. The majority of the dose recovered in feces exists as the M5 metabolite, with only 0.2% excreted unchanged as the parent compound. Less than 1.5% of the dose recovered in urine and feces is the M1 metabolite. Finalidomide is not expected to be metabolized by the gut microbiota. The steady-state volume of distribution of finalidomide is 52.6 L. The systemic clearance of finalidomide is approximately 25 L/h. Metabolites/Metabolic Substances: Approximately 90% of finalidomide is metabolized by CYP3A4, and 10% by CYP2C8. CYP1A1 contributes little to its metabolism. Finalidomide has no active metabolites. Finalidomide is aromatized by CYP3A4 and CYP2C8 to generate metabolite M1, which is further hydroxylated by CYP3A4 to generate metabolite M2, and finally oxidized by CYP3A4 to generate metabolite M3. In addition, finalitones can also be epoxidized by CYP3A4 and CYP2C8, and may be hydrolyzed to generate metabolite M4. M4 is then hydroxylated by CYP3A4 to generate metabolite M5, and oxidized to generate metabolite M8. Finalitones can also be hydroxylated by CYP2C8 to generate metabolite M7, and further oxidized to generate metabolite M9. Metabolite M10 is generated from finalitones via demethylation, oxidation, and ring-opening reactions. Metabolite M13 is generated by the deethylation of finalitones by CYP1A1, while metabolite M14 is generated by a multi-step reaction involving CYP2C8 and CYP3A4; the specific mechanism of this process is not yet clear.

---

Biological Half-Life
In four healthy men, the half-life of 10 mg finalitones in plasma was 17.4 hours, and the half-life in whole blood was 12.3 hours. The terminal half-life of finalitones is approximately 2-3 hours.

Hepatotoxicity
In placebo-controlled trials involving thousands of patients, elevated serum enzymes or hepatotoxicity are generally not mentioned. In the largest placebo-controlled trials, the incidence of hepatobiliary adverse events was similar in the fenelazol and placebo groups (4.4% vs 4.8%), and no serious hepatic adverse events were reported. Since its approval and widespread use, fenelazol has not been associated with cases of acute liver injury, and elevated aminotransferases or clinically significant liver injury are not mentioned in the potential adverse event list in the product information. Probability Score: E (Unlikely to be a cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information regarding the use of fenelazol during lactation. Fenelazol binds to plasma proteins at a rate of 92%, so the concentration in breast milk may be low. However, the manufacturer recommends avoiding breastfeeding during treatment and for one day after treatment.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

---

Protein binding
Finelone has a 92% protein binding rate in plasma, primarily binding 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
Fennellone is a nonsteroidal mineralocorticoid receptor antagonist indicated for reducing the risk of persistently declining glomerular filtration rate, end-stage renal disease, cardiovascular death, heart attack, and hospitalization for heart failure in adult patients with chronic kidney disease and type 2 diabetes. Because it only requires once-daily administration, its duration of action is moderate; and because the dosage range in clinical trials was 1.25 mg to 80 mg, it has a wide therapeutic window. Patients should be informed of 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.

---

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.

---

View More

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.

---

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