April 1, 1988Journal of Cardiovascular Pharmacology
Pharmacokinetics and Thrombolytic Properties of a Nonglycosylated Mutant of Human Tissue-Type Plasminogen Activator, Lacking the Finger and Growth Factor Domains, in Dogs with Copper Coil-Induced Coronary Artery Thrombosis
Key result
Novel variant t-PA improves half-life and thrombolytic efficacy over natural t-PA in preclinical coronary thrombosis.
- n=13
Why the study?
The pharmacokinetics and thrombolytic properties of a nonglycosylated mutant of human tissue-type plasminogen activator lacking the finger and growth factor domains were studied to evaluate its efficacy in coronary artery thrombosis.
Population
Dogs with copper coil-induced thrombosis of the left anterior descending coronary artery
Comparison
t-PA-delta FE3X variant vs natural t-PA (Mel-t-PA)
Design
Preclinical study with bolus injections in groups of dogs
Follow-up
3 hours
Authors
Discussion
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Implication
Animal study of t-PA variant supports further development; leaves open translation to human coronary thrombolysis.
Structured PICO
P
Population
13 dogs with copper coil-induced coronary artery thrombosis treated with bolus injections of a t-PA variant or natural t-PA.
I
Intervention
t-PA-delta FE3X (variant of human tissue-type plasminogen activator) bolus injection over 2 min at 0.15 mg/kg, 0.075 mg/kg, or 0.038 mg/kg
C
Comparator
Natural t-PA (Mel-t-PA) bolus injection at 0.1 mg/kg
O
Outcome
Pharmacokinetics (plasma peak levels, half-life, clearance) and reperfusion time within 3 hourssurrogate
A nonglycosylated mutant of human t-PA lacking finger and growth factor domains demonstrated a longer half-life and higher thrombolytic efficacy than natural t-PA in a canine model of coronary thrombosis.
Cite This Study
Cambier et al. (1988) studied Copper coil-induced coronary artery thrombosis (n=13). t-PA-delta FE3X vs. Natural t-PA (Mel-t-PA) 0.1 mg/kg was evaluated on Coronary artery reperfusion. The variant t-PA-delta FE3X had a markedly longer plasma half-life and higher thrombolytic efficacy than natural t-PA when administered as a bolus injection in dogs with coronary thrombosis.