Thrombin alfa API Manufacturers

General Description:

Thrombin alfa, identified by CAS number 869858-13-9, is a notable compound with significant therapeutic applications. Thrombin Alfa is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Thrombin Alfa is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Thrombin Alfa precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Thrombin Alfa has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of Thrombin Alfa employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance. The thrombin alfa product ultimate comes from recombinant human prethrombin-1 . Nevertheless, because the incidence of hemostasis within a timely manner is relatively comparable between the use of thrombin alfa and the placebo treatment in patient subjects, thrombin alfa is not currently approved by certain organizations like the European Medicines Agency .

Indications:

This drug is primarily indicated for: Indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age . Additionally, thrombin alfa can be used in conjunction with an absorbable gelatin sponge, USP . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Thrombin alfa undergoes metabolic processing primarily in: Much like endogenous thrombin, thrombin alfa does not circulate in the blood as a free, active molecule for very long . After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) . This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Thrombin alfa are crucial for its therapeutic efficacy: Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa . Nevertheless, observations of a subcutaneous administration of 350 U rhThrombin/kg resulted in a bioavailability of approximately 95% in male cynomolgus monkeys . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Thrombin alfa is an important consideration for its dosing schedule: Following intravenous administration, thrombin alfa exhibited an initial half-life of 0.17 hours (10.2 min) . Following either intravenous or subcutaneous administration, the agent demonstrated a terminal half-life of about 15 hours . This data follows administration of thrombin alfa to cynomolgus monkeys. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Thrombin alfa exhibits a strong affinity for binding with plasma proteins: Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa . Protein binding data is subsequently not readily available, although thrombin alfa functions predominantly to interact with a very specific set of clotting factors - a function that endogenous thrombin (of which thrombin alfa is a recombinant replica of) is naturally designed to perform. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Thrombin alfa from the body primarily occurs through: Thrombin alfa, like endogenous thrombin, is cleared by two primary separate pathways: (1) through rapid formation of thrombin inhibitor complexes, which are recognized by hepatic receptors and degraded, and (2) via direct binding to thrombomodulin on the endothelium, followed by internalization and degradation . Specific thrombin inhibitors include ATIII, alpha-2M and heparin cofactor II . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Thrombin alfa is distributed throughout the body with a volume of distribution of: Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa . Volume of distribution data is subsequently not readily available. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Thrombin alfa is a critical factor in determining its safe and effective dosage: Traditional absorption, distribution, metabolism, and excretion studies were not/have not been performed for thrombin alfa . Regardless, thrombin alfa, like natural thrombin, is known to be rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Thrombin alfa exerts its therapeutic effects through: As thrombin alfa, a recombinant thrombin, is considered to be identical in amino acid sequence and structural similarity to naturally occurring human thrombin, it is believed that thrombin alfa shares the same pharmacodynamics as endogenous or natural human thrombin coagulation factor . In the natural blood coagulation pathway of the human body, thrombin functions as a coagulation factor that converts clotting factor XI to XIa, factor VIII to VIIIa, V to Va, fibrinogen to fibrin, and XIII to XIIIa . Specifically, clotting factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between the lysine and glutamine residues found in fibrin. These covalent bonds assist in increasing the stability of the fibrin clot . Additionally, thrombin also promotes the activation and aggregation of platelets by way of activating protease-activated receptors on the cell membranes of platelets . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Thrombin alfa functions by: Specifically, thrombin alfa is a human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding . In particular, thrombin alfa activates platelets and cleaves fibrinogen to fibrin, leading directly to clot formation. It also activates clotting factor XIII, leading to fibrin cross-linking and clot stability . The ability of thrombin alfa to bypass the initial enzymatic steps of the coagulation pathway provides a clear rationale as to why thrombin alfa may be used as a topical haemostatic agent . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Thrombin alfa belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Thrombin alfa is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Biological Factors, Blood Coagulation Factors, Blood Proteins, Endopeptidases, Enzymes, Enzymes and Coenzymes, Hemorrhage, Hemostatics, Hydrolases, Increased Coagulation Factor Activity, Peptide Hydrolases, Proteins, Serine Endopeptidases, Serine Proteases. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.