关键词: 重组E. coli L-天冬酰胺酶, 药代动力学

Abstract: The distribution of 125I recombinant E .coli L-asparaginase in tissues or organs and the excretion in urine, feces and bile were studied with in vivo radioactive tracer technique. The amount of radioactivity excreted in urine, feces and bile within 24 h after intravenous administration of 125I recombinant E .coli L-asparaginase to rats was 68.95%,4.44% and 5.36% of the dose respectively.125I recombinant E .coli L-asparaginase in plasma samples was determined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGE and bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model dependent method. The concentration time curves of recombinant E .coli L-asparaginase after intravenous injection at 1250 IU·kg^-1, 2500 IU·kg^-1, 5000 IU·kg^-1 to rats were consistent with the two compartment model. The first and terminal elimination t1/2 were 0.52~0.63h and 2.39~2.76h respectively. AUC was linearly related to the doses. The results of distribution in tissues or organs and excretion in urine suggested that the metabolites of the enzyme were cleared by mechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E .coli L asparaginase in rats are warranted for the design of future clinical trials.

Key words: Pecombinant E.coli L-asparaginase, Pecombinant E.coli L-asparaginase, Pharmacokinetics, Pharmacokinetics