Since the medial lethal dose (LD 50 ) of rhprouk was not detected from either a single intraceous
injection or an intraperitiounal
one the lethal dose (LD) of rhprouk was investigated in mice. Our data indicates that the LD was above 9×10 7 IU/kg via either a single intravenous
injection or a single intraperitoneal injection of rhpro-UK in mice. In four random assigned groups of monkeys (2 males and 2 females in each group), rhprouk was infused intravenously for 14 days at a daily dose of 3.6×10 5 IU/kg, 6.75×10 5 IU/kg, 13.5×10 5 IU/kg, and 27×10 5 IU/kg respectively. No monkey was found dead during the experiment. During the
treatment and recovery periods of the dose group of 3.6×10 5 IU/kg rhprouk, the behavior and motor activities of monkey subjects were normal. The body weight, excretion, food intake, ECG, blood status, skin observation, urine and feces examination did not change significantly after the drug application. Compared with the control group receiving saline or vehicle treatments, there was no pathological changes caused by drugs in the organ and tissue samples of the experimental subjects in the 14 day rhprouk treatment period. However, in dose groups of 6.75×10 5 IU/kg, 13.5×10 5 IU/kg, and 27×10 5 IU/kg, we observed the drug related subcutaneous hemorrhage, congestion, purpura, positive feces and urine blood test, anemia and tachycardia in experimental subjects. The immunological examination revealed that a minor amount of prouk antibody was detected in the serum during the treatment and recovery period. Therefore our data indicated that the sub lethal dose of rhprouk was no lower than 3.6×10 5 IU/kg.