Thrombolysis of canine femoral artery thrombus by a novel modified tissue-type plasminogen activator (E6010).
The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper coil-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of various thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E6010 was identical to that of continuous intravenous infusion of recombinant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic agents. On the other hand, administration of the thrombolytic agents dose-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with administration of E6010, and therefore we concluded that E6010 is unlikely to cause bleeding complications after administration.
Suzuki
N
N
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Suzuki
S
S
Nagaoka
N
N
Mizuo
H
H
Yuzuriha
T
T
Yoshitake
S
S
Kanmatuse
K
K
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005263:Femoral Artery; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects; D007275:Injections, Intravenous; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C076356:E 6010; D004815:Epidermal Growth Factor; D010959:Tissue Plasminogen Activator