Abstract: Objective To characterize the pharmacokinetics, tissue distribution, and excretion profiles of recombinant human endostatin(rhEndostatin) following a single intravenous administration to rats. Methods The rhEndostatin was labeled with ¹²⁵I and the pharmacokinetics of ¹²⁵I-rhEndostatin was investigated by two assays: the total radioactivity assay(RA method) and the radioactivity assay after precipitation with trichloroacetic acid(TCA-RA method). Results The rats were randomly assigned into three groups in which the rats were given intravenously rhEndostatin at doses of 5, 10 and 20 mg/kg, respectively. The serum rhEndostatin concentrations and the area under the concentration-time curve(AUC) increased with the dose increment. The serum elimination half-life(t_1/2β) and clearance(CL) did not display markedly dose-dependence and were relatively consistent in the range of 243~265 min and 2.4~2.6 mL·kg^-1·min^-1 using TCA-RA method, respectively. In the rats with 10 mg/kg rhEndostatin(iv), the levels were the highest in the kidneys, and the lowest in the brain, muscle and adipose tissue. The accumulative excretion percentages of ¹²⁵I-rhEndostatin from urine and feces reached 86.9% and 5.8% of the administered radioactivity within 96 h, and 1.3% from bile within 24 h, respectively. Conclusion RhEndostatin has linear pharmacokinetic properties within the therapeutic dose range. The rhEndostatin has characteristics of targeting special tissue distribution(the highest level of the drug was found in the kidneys), which may reflect that urinary excretion is the dominant route of elimination via the kidneys in rats following iv administration of rhEndostatin.

Key words: recombinant human endostatin, pharmacokinetics, tissue distribution, excretion, rat