| Drug Name: |
Ecallantide |
| Applications: |
Indicated for the symptomatic treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older. |
| Examples of Clinical Use: |
Acute attacks of hereditary angioedema (HAE) |
| Pharmacodynamics: |
Intravenous administration of the product doses ≥20 mg/m^2 resulted in prolongation of activated partial thromboplastin time (aPTT) without an indication of bleeding. The product administration has been associated with instances of arrhythmia. In a clinical trial of patients experiencing acute attacks of hereditary angioedema (HAE), intravenous administration of the product demonstrated a significant improvement in symptoms affecting the oropharynx, abdomen, gastrointestinal tract, and limbs within 4 hours post-administration compared to placebo. A substantial decrease in the severity and duration of attacks was also observed in patients with moderate-to-severe HAE attacks. In clinical trials, the product had no significant effect on the QTc interval, heart rate, or any other components of the ECG. |
| Mechanism of action: |
The kallikrein-kinin system is a complex proteolytic cascade that promotes inflammatory and coagulation pathways. Human plasma kallikrein acts as a protease to mediate the conversion of High Molecular Weight (HMW) kininogen to bradykinin, which is a vasoactive mediator that increases vascular permeability and induces localized swelling, inflammation, and pain. The actions of kallikrein is regulated by the major endogenous inhibitor, C1-esterase-inhibitor (C1-INH). C1-INH also functions to regulate the activation of the complement and intrinsic coagulation (contact system pathway), which also initiates the production of bradykinin. Upon audoactivation via exposure to negatively charged surfaces, factor XII promotes the generation of factor XIIa and kallikrein. C1-INH inhibits both factor XIIa and kallikrein. Kallikrein may in turn reciprocally activate more FXII. Hereditary angioedema is associated with a deficiency of the C1 inhibitor is caused by a mutation in the C1 INH gene. Resulting effect is excessive production of the vasodilator, bradykinin. The actions of bradykinin produce typical edematous signs and symptoms of hereditary angioedema by enhancing vascular and endothelial permeability, leading to increased outflow of plasma into the interstitium to produce local edema. |
| Affected organisms: |
Humans and other mammals |
| Targets: |
Target 1. Plasma kallikrein |
