在慕尼黑 Wistar Frömter (MWF) 大鼠中，finerenone (BAY 94-8862) 显着降低收缩压 (SBP) 并将蛋白尿减少超过 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
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.

---

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.

---

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).

---

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.

---

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

111.25

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)

配方 1 中的溶解度: ≥ 2.08 mg/mL (5.50 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

配方 2 中的溶解度: ≥ 1.93 mg/mL (5.10 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 19.3 mg/mL的澄清DMSO储备液加入到400 μL PEG300中并混合均匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 1.93 mg/mL (5.10 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 19.3 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。