Human thrombin API Manufacturers

General Description:

Human thrombin, identified by CAS number 9002-04-4, is a notable compound with significant therapeutic applications. Human thrombin is a sterile solution, pH 6.8-7.2, containing highly purified human thrombin for the activation of clotting. Thrombin is a highly specific serine protease encoded by the F2 gene that transforms soluble fibrinogen into insoluble fibrin. This transformation mimics the final coagulation cascade step which involves the clotting mass that adheres to the wound surface and achieves hemostasis and sealing of open tissues. In particular, while human thrombin products are made from pooled human source plasma, recombinant thrombin is a human coagulation protein produced via recombinant DNA technology from a genetically modified Chinese hamster ovary cell line . Furthermore, human thrombin is manufactured by chromatographic purification of prothrombin from cryo-poor plasma followed by activation with calcium chloride .

Indications:

This drug is primarily indicated for: Human thrombin is indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules are accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical. In combination with fibrinogen, it is used indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Human thrombin undergoes metabolic processing primarily in: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Nevertheless, commercial human thrombin products are expected to be metabolized in the same way as endogenous thrombin is. Endogenous thrombin 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 Human thrombin are crucial for its therapeutic efficacy: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Particularly because the agent is topical, systemic absorption is expected to be small . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Human thrombin is an important consideration for its dosing schedule: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Human thrombin exhibits a strong affinity for binding with plasma proteins: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Protein binding data is subsequently not readily available, although human thrombin functions naturally to interact with a very specific set of clotting factors. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Human thrombin from the body primarily occurs through: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Nevertheless, commercial human thrombin products are expected to act in much the same way as endogenous thrombin does. Natural bodily 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:

Human thrombin is distributed throughout the body with a volume of distribution of: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Precisely because human thrombin is applied only topically, systemic exposure or distribution to other organs and tissues is not expected . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Human thrombin is a critical factor in determining its safe and effective dosage: Due to the nature of the product, which is intended for topical application to the surface of the tissue at the surgical site, pharmacokinetic studies were not conducted . Regardless, commercial human thrombin, like endogenous thrombin, is generally 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:

Human thrombin exerts its therapeutic effects through: Clinical pharmacodynamic studies with human thrombin have not been performed at this time . Regardless, commercial human thrombin products are expected to demonstrate activity that is identical to thrombin found endogenously in the body. 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:

Human thrombin functions by: Human thrombin (coagulation factor IIa) is a highly specific protease that transforms plasma fibrinogen into fibrin which, in the presence of clotting factor XIII in the patient's plasma, is cross-linked to form a stable clot . When applied to a surgical wound where bleeding is present, thrombin activates fibrinogen in the patient's plasma to form fibrin, which results in clot formation and hemostasis . The fibrin clot is stabilized by cross-linking occurring as a result of activation of the patient's endogenous factor XIII, which requires the presence of calcium . Human thrombin does not require any intermediate physiological agent because it naturally clots the fibrinogen of the blood directly . Any failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself . The speed with which human thrombin clots blood is dependent upon the concentration of both the human thrombin used and fibrinogen present . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Human thrombin 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:

Human thrombin is categorized under the following therapeutic classes: Blood Coagulation Factors, Increased Coagulation Factor Activity. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.