Profibrinolysin
Profibrinolysin Uses, Dosage, Side Effects, Food Interaction and all others data.
Profibrinolysin is a pro-enzyme (i.e. a zymogen) which is cleaved to form plasmin - also known as fibrinolysin - 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.
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.
| Trade Name | Profibrinolysin |
| Generic | Plasminogen |
| Plasminogen Other Names | 1-glutamylplasminogen, Human plasminogen, Plasma trypsinogen, plasminogen, human-tvmh, Profibrinolysin |
| Type | |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Profibrinolysin is plasma-derived human plasminogen administered intravenously to treat type 1 plasminogen deficiency (hypoplasminogenemia).
Plasma-derived human plasminogen, marketed under the brand name Ryplazim, is indicated for the treatment of patients with plasminogen deficiency type 1 (hypoplasminogenemia).
Profibrinolysin is also used to associated treatment for these conditions: Type I Plasminogen Deficiency.
How Profibrinolysin works
Profibrinolysin 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. Ryplazim) 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.
Toxicity
There are no data regarding overdose of intravenously administered human plasminogen.
Food Interaction
No interactions found.Volume of Distribution
The mean steady-state volume of distribution of Ryplazim is approximately 49.3 mL/kg.
Elimination Route
Following 12 weeks of intravenous administration every 2 to 4 days, the mean AUCinf of Ryplazim was 5731.8 hr*% and its Cmax 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.
Half Life
The mean half-life of Ryplazim at steady-state is approximately 39.2 hours.
Clearance
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.
Innovators Monograph
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