C1 ESTERASE INHIBITOR (C1INH) IS A NORMAL CONSTITUENT OF HUMAN BLOOD AND IS ONE OF THE SERINE PROTEASE INHIBITORS (SERPINS). THE PRIMARY FUNCTION OF C1INH IS TO REGULATE THE ACTIVATION OF THE COMPLEMENT AND CONTACT SYSTEM PATHWAYS. REGULATION OF THESE SYSTEMS IS PERFORMED THROUGH THE FORMATION OF COMPLEXES BETWEEN THE PROTEASE AND THE INHIBITOR, RESULTING IN INACTIVATION OF BOTH AND CONSUMPTION OF THE C1INH.
C1INH EXERTS ITS INHIBITORY EFFECT BY IRREVERSIBLY BINDING SEVERAL PROTEASES (TARGET PROTEASES) OF THE CONTACT AND COMPLEMENT SYSTEMS. THE EFFECT OF RUCONEST ON THE FOLLOWING TARGET PROTEASES WAS ASSESSED IN VITRO: ACTIVATED C1S, KALLIKREIN, FACTOR XIIA AND FACTOR XIA. INHIBITION KINETICS WERE FOUND TO BE COMPARABLE WITH THOSE OBSERVED FOR PLASMA-DERIVED HUMAN C1INH.
HAE PATIENTS HAVE LOW LEVELS OF ENDOGENOUS OR FUNCTIONAL C1INH. ALTHOUGH THE EVENTS THAT INDUCE ATTACKS OF ANGIOEDEMA IN HAE PATIENTS ARE NOT WELL DEFINED, IT IS THOUGHT THAT CONTACT SYSTEM ACTIVATION, AND RESULTING INCREASED VASCULAR PERMEABILITY LEAD TO THE CLINICAL MANIFESTATION OF HAE ATTACKS. SUPPRESSION OF CONTACT SYSTEM ACTIVATION BY C1INH THROUGH THE INACTIVATION OF PLASMA KALLIKREIN AND FACTOR XIIA IS THOUGHT TO MODULATE VASCULAR PERMEABILITY BY PREVENTING THE GENERATION OF BRADYKININ.