Plasminogen API Manufacturers

General Description:

Plasminogen, identified by CAS number 9001-91-6, is a notable compound with significant therapeutic applications. Plasminogen is a pro-enzyme (i.e. a zymogen) which is cleaved to form plasmin - also known as - as part of the fibrinolytic pathway that breaks down fibrin blood clots. This pathway is activated when a clot is no longer needed or to prevent a clot from extending beyond the site of injury. In June 2021, the FDA approved a plasma-derived plasminogen (Ryplazim, human plasminogen-tvmh) for the treatment of type 1 plasminogen deficiency (hypoplasminogenemia). It is the first and only FDA-approved treatment for this condition, which causes wood-like lesions to form on the mucous membranes of patients, providing an unmet medical need for patients with this rare congenital disease.

Indications:

This drug is primarily indicated for: Plasma-derived human plasminogen, marketed under the brand name Ryplazim, is indicated for the treatment of patients with plasminogen deficiency type 1 (hypoplasminogenemia). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Plasminogen undergoes metabolic processing primarily in: Plasminogen is a zymogen which is converted into the active fibrinolytic plasmin, or fibrinolysin, by tissue plasminogen activator (tPA) or urokinase-like plasminogen activator (uPA). This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Plasminogen are crucial for its therapeutic efficacy: Following 12 weeks of intravenous administration every 2 to 4 days, the mean AUC_inf of Ryplazim was 5731.8 hr*% and its C_max was approximately 125% of the mean physiological level (normal: 70-130%). After 12 weeks of therapy, physiological plasminogen levels were sustained for approximately 24 hours post-dose and patients maintained a 10% absolute increase in plasminogen concentration for up to 96 hours after administration. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Plasminogen is an important consideration for its dosing schedule: The mean half-life of Ryplazim at steady-state is approximately 39.2 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Plasminogen is distributed throughout the body with a volume of distribution of: The mean steady-state volume of distribution of Ryplazim is approximately 49.3 mL/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Plasminogen is a critical factor in determining its safe and effective dosage: The clearance of Ryplazim appears to slow with extended use. Following the first intravenous dose the mean clearance of Ryplazim was 1.4 mL/hr/kg, while following an intravenous dose at week 12 the mean clearance was 0.9 mL/hr/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Plasminogen exerts its therapeutic effects through: The intravenous administration of plasminogen temporarily increases levels of plasminogen in the blood, allowing for the reduction or resolution of the lignous lesions associated with plasminogen deficiency. Therapy is administered periodically, every 2 to 4 days, to prevent any significant build-up of these lesions between doses. Plasminogen administration can lead to tissue sloughing at mucosal sites where lignous lesions have built up, which may lead to organ or airway obstruction depending on the site of the lesion(s). Patients should be monitored for at least 4 hours post-administration, especially patients with evidence of airway involvement, to ensure airway management and respiratory support is readily available. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Plasminogen functions by: Plasminogen is a zymogen produced in the liver which, when cleaved into its active form, breaks down fibrin blood clots. This active form, called plasmin or fibrinolysin, is generated when tissue plasminogen activator (tPA) or urokinase-like plasminogen activator (uPA) cleave plasminogen to begin the fibrinolytic pathway. Blood clots are broken down by plasmin into soluble fibrin and fibrinogen degradation products when the clot is no longer needed. Type 1 plasminogen deficiency, also called hypoplasminogenemia, is a congenital disorder in which patients are deficient in plasminogen. Interestingly, this disease does not increase the risk of clotting, but rather results in the formation of lignous pseudomembranous lesions on the mucous membranes of the body. Lesions range in location and severity but can lead to severe long-term consequences if left untreated. For example, lignous conjunctivitis, the most common manifestation of type 1 plasminogen deficiency, may lead to corneal tearing and blindness. Human plasminogen is administered topically (e.g. in eye drops) or intravenously (i.e. (https://www.fda.gov/media/149806/download)) in order to temporarily increase local or serum levels of fibrinogen. When this therapy is administered every 2 to 4 days, it prevents the build-up of lignous lesions and allows existing lesions to be shed. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Plasminogen 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:

Plasminogen is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anticoagulants, Beta-Globulins, Blood Proteins, Cardiovascular Agents, Enzyme Precursors, Enzymes and Coenzymes, Fibrin Modulating Agents, Fibrinolytic Agents, Globulins, Hematologic Agents, Protein Precursors, Proteins, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.