Investigation of Pharmacodynamics, Pharmacology, and Toxicology of Domestic Human Prourokinase

Abstract

The comparison of the effect of fibrinolytic activity of recombinant human prourokinase (rhpro-UK) and urokinase(UK) with rabbits indicated rhpro-UK and UK all decreased resolution time of globular proteins, and the affect of rhpro-UK on parameter of fibrinolysis of rabbits was less than UK. The solution of thrombin of rhpro-UK in vitro was increased with dosage of rhpro-UK, and when rhpro-UK was compared with isodose UK, the difference is significant. Both rhpro-UK and UK all was marked solution of thrombin from Chinese piglets, and it were not evident effect on fibrinogen, plasminogen, and a2-antiplasmin of the piglets. The affect of rhpro-UK on bleeding time, clotting time, bleeding amount of unit time was less than UK. It indicated that the side effect of rhpro-UK was distinguished less than UK. The investigation of pharmacology of ileums of mice, rats, dogs, and guinea pigs indicated that rhpro-UK was not marked affect on behavior, state, central nervous system, cardiovascular system, respiratory system, and digestive system of the tested animals. But tested dogs were bleeding at location of operation, and the blood of the animal was heparinized. The studis of toxicology of rhpro-UK indicated that rhpro-UK was median lethal dose of 97.5 mg/kg in mice. When The Beagle dogs was administed rhpro-UK of 2, 8, 28 mg/kg, the toxic reaction was not observed, except for temporal hyperemia of gum, extend of clotting time, increasing of total cholerythrin, total proteins, albumin of the dogs, the direct damage of organs for the medicine was not observed in examination of pathology in the dosages of 8 and 28 mg/kg, any toxic reaction was not observed in dosage of 2 mg/kg. The special toxic experiments proved that rhpro-UK was not of mutagenesis and teratogenesis.