TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats.
TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation.
Motoyama
Y
Y
Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakata
Y
Y
Seki
J
J
Sato
M
M
Namikawa
Y
Y
Horiai
H
H
Ono
T
T
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C054546:TFC 612; D000527:Alprostadil