Half-life,tissue distribution and excretion of human tissue urokinase type plasminogen activator after single-dose intravenous injection in rats

Objective To evaluate the half-life,tissues distribution and excretion of human tissue urokinase type plasminogen activator(HTUPA) in SD rats.Methods Using 125I labeled HTUPA as a tracer,the samples of plasma,tissue,bile,urine and fecal were collected from the test rats at the various time points with various dosage after single-dose intravenous injection and measured by counting TCA-precipitable radioactivity.Half-life,tissue distribution and excretion rate were evaluated.Results The concentration-time curve of HTUPA was fitted to a two-compartment model after intravenous injection with the dosages of 1,2 and 4 mg/kg,respectively;with the mean distribution half life(t1/2a) of(5.62±4.22),(6.37±4.93) and(6.57±4.13) min,respectively;Also,blood clearance showed elimination half life(t1/2b) of(49.21±19.36),(41.17±18.50) and(43.68±28.67) min,respectively.A linear relationship was found between the dose and area under the curve(AUCinf) with r=0.998 5.After the rats being injected with HTUPA of 2 mg/kg,the concentration of the HTUPA was higher in kidney and liver,and was lower in brain.Additionally,the excretion ratios of the HTUPA into urine and feces at 96 h were 79.08% and 15.40%,respectively,and it was 6.67% in bile at 24 h.Conclusion As a new candidate of thrombolytic drug,HTUPA has faster distribution speed and appropriate half life.