What Is Levosimendan?

Levosimendan (Simendan) is a drug for treating heart failure. Its molecular formula is C14H12N6O. The chemical name of Levosimendan is: (R)-[[4- (1,4,5,6-tetrahydro-4) -Methyl-6-oxo-3-pyridazinyl) phenyl] -hydrazino] -malononitrile.

The medicine is a yellow or orange-yellow clear liquid, which is a sterilized anhydrous ethanol solution of levosimendan, which also contains hydroxypropylbetacyclodextrin and anhydrous citric acid.

Chinese name: Zosimundan
Foreign name: Simendan

Molecular formula: C14H12N6O
Molecular weight: 280.28

Levosimendan indications

This product is suitable for short-term treatment of acute decompensated heart failure (ADHF) with poor efficacy of traditional therapies (diuretics, angiotensin-converting enzyme inhibitors and digitalis) and requiring increased myocardial contractility.

Levosimendan molecular structure diagram

Levosimendan Chinese alias: (R)-(-)-[[4- (1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl) phenyl] -Hydrazine] malononitrile

English alias : ((4- (1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl) phenyl) hydrazono) propanedinitrile; 2-[[4- (4-Methyl-6-oxo -4,5-dihydro-1H-pyridazin-3-yl) phenyl] hydrazinylidene] propanedinitrile

CAS RN : 131741-08-7

Molecular structure diagram ^[1]

Zuo Mengdan classification name

Primary classification: Circulatory drugs. Secondary classification: Anticardiac insufficiency drugs. Third classification: Other.

English name of Levosimendan

Levosimendan

Levosimendan drug alias

Simdax

Pharmacological effects of Levosimendan

This product is a calcium ion sensitizer that works by altering calcium binding information transmission. This product is directly combined with troponin to stabilize the spatial configuration of myocardial fibrin necessary for calcium-induced myocardial contraction, thereby increasing myocardial contractility without significant changes in heart rate and cardiac oxygen consumption. At the same time, this product has a strong vasodilator effect, which activates adenosine triphosphate (ATP) -sensitive potassium channels to expand blood vessels. This product mainly expands peripheral veins and reduces the preload of the heart. When this product is used in large doses, it has a certain phosphodiesterase inhibitory effect, which can increase the cAMP concentration in myocardial cells and exert an additional positive muscle effect.

Levosimendan Pharmacokinetics

This product can be absorbed from the intestine quickly and has high bioavailability. After oral administration of 14C labeled drugs, high radioactivity can be measured in the digestive tract, liver, kidney, and urine, indicating that drugs and their metabolites are widely distributed in these tissues, but the radioactivity measured in brain tissue is very low , Suggesting that drugs are more difficult to penetrate the blood-brain barrier. The drug is completely metabolized in the human body, and only trace amounts of the prototype drug are detected in urine and feces. The biotransformation of drugs in the human body is mainly the binding of glutathione in the liver. The conjugate is unstable and quickly converts to cysteine and cysteyl derivatives. These substances are biologically active and are the main metabolites of the drug in urine. This product can also be reduced by the intestinal flora, and the amino derivative (OR-1855) produced can be further acetylated to OR-1896 before being excreted in the feces. OR-1855 and OR-1896 have a long elimination half-life and can prolong the hemodynamic effect of the drug. Drugs are excreted mainly through urine and bile. The drug metabolites appearing in urine are cysteine and a combination of cysteine glycine and drugs. Only a small amount of the original drug is found in urine.

Levosimendan indication

This product is used for the treatment of heart failure.

Levosimendan contraindications

Those who are allergic to this product are prohibited.

Leximendan notes

This product can be reduced orally by the intestinal flora, and the reduction product participates in the enterohepatic circulation and has similar biological activity as levosimendan, which increases the incidence of side effects such as headache and dizziness.

Levosimendan adverse reactions

Adverse reactions were rare, with occasional headaches, dizziness, and palpitations.

Levosimendan dosage

1. Oral: 1 ~ 4mg each time, 2 ~ 4 times daily. 2. Intravenous: Dilute with 5% dextrose, start by injecting at a loading dose of 12 ~ 24g / kg for 10min, and then instill at 0.1g / (kg · min). After 30 to 60 minutes of medication, observe the efficacy of the drug, and the drip rate can be adjusted to 0.2 to 0.5 g / (kg · min). A 6 to 24 h infusion is recommended.