MIRel™ (Reteplase) is
a single chain deletion mutant of alteplase
that is expressed in Escherichia coli
and, therefore, is expressed as an unglycosylated
protein (355 amino acids) with a total
molecular weight of 39 kDa.
The molecule consists of cringle 2 and
the protease domain of the alteplase molecule.
Because of the deletion of the fibronectin
finger region, the binding of reteplase
to fibrin is significantly reduced in
comparison with that of alteplase. Although
kringle 2 (known to stimulate protease
in the presence of fibrin) is part of
the reteplase molecule, reteplase is stimulated
in the presence of fibrin to a lower extent
than alteplase, suggesting that the fibronectin
finger is involved in the stimulation
of the protease as well.
Reteplase, in comparison with alteplase,
is characterised by reduced fibrin selectivity.
In the abscence of fibrin, reteplase and
alteplase do not differ with respect to
their activity as plasminogen activators,
nor do they differ with respect to their
inhibition by the plasminogen activator
inhibitor type 1 (PAI-1).
The elimination of reteplase from the
circulating plasma predominantly occurs
in the liver. Because of the deletion
of the fibronectin finger region, the
epidermal growth factor domain and kringle
1, as well as the carbohydrate side chains,
the hepatic elimination of the molecule
is reduced. Consequently, plasma half
life is increased to 14-18 minutes (versus
3-4 minutes with alteplase).
This allows reteplase to be administered
as boli (versus as an initial bolus followed
by an infusion, as with alteplase). The
best results have been obtained with a
double bolus of 10 U each 30 minutes apart
in the case of an acute myocardial infarction.
Reteplase was superior to alteplase (administered
over three hours) with respect to patency
of the infarct related coronary artery.
With reteplase patency was reached earlier
and more frequently than with alteplase.
Each kit of MIRel contains two vials of
10 units of Reteplase each, sterile water
for injection, two syringes and four needles