Nafamostat API Manufacturers

General Description:

Nafamostat, identified by CAS number 81525-10-2, is a notable compound with significant therapeutic applications. Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.

Indications:

This drug is primarily indicated for: Used as an anticoagulant in patients with disseminative blood vessel coagulation, hemorrhagic lesions, and hemorrhagic tendencies. It prevents blood clot formation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Nafamostat undergoes metabolic processing primarily in: Nafamostat is mainly hydrolyzed by hepatic carboxyesterase and long-chain acyl-CoA hydrolase in human liver cytosol. Main metabolites are p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN) as inactive protease inhibitors. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Half-life:

The half-life of Nafamostat is an important consideration for its dosing schedule: Approximately 8 minutes. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Nafamostat from the body primarily occurs through: Two metabolites of NM, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN), are renally excreted. Nafamostat accumulates in the kidneys. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Pharmacodynamics:

Nafamostat exerts its therapeutic effects through: Nafamostat is a fast-acting proteolytic inhibitor used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin by competitively inhibiting several serine proteases including thrombin. It improves acute pancreatitis and prevents blood clot formation during extracorporeal circulation and has an anti-inflammatory effect in vitro. A study suggets that nafamostat has a neuroprotective role during ischemia-induced brain injury from antithrombin activity . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Nafamostat functions by: Nafamostat mesilate inhibits various enzyme systems, such as coagulation and fibrinolytic systems (thrombin, Xa, and XIIa), the kallikrein–kinin system, the complement system, pancreatic proteases and activation of protease-activated receptors (PARs) . Nafamostat inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)-6 and IL-8 levels in cultured human trophoblasts. It is shown to act as an antioxidant in TNF-α-induced ROS production . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Nafamostat belongs to the class of organic compounds known as guanidinobenzoic acids and derivatives. These are aromatic compounds containing a guanidine group linked to the benzene ring of a benzoic acid (or a derivative thereof), classified under the direct parent group Guanidinobenzoic acids and derivatives. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Benzene and substituted derivatives class, specifically within the Benzoic acids and derivatives subclass.

Categories:

Nafamostat is categorized under the following therapeutic classes: Amidines, Analgesics, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Anticoagulants, Antirheumatic Agents, Complement Inactivating Agents, Enzyme Inhibitors, Fibrinolysin, antagonists & inhibitors, Hematologic Agents, Immunologic Factors, Kallikreins, antagonists & inhibitors, OCT1 substrates, OCT2 Substrates, Peripheral Nervous System Agents, Protease Inhibitors, Sensory System Agents, Serine Protease Inhibitors, Trypsin Inhibitors. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.