Pharmacokinetics of human urinary kallidinogenase in rabbits and rats

LIU Xiuwen, TANG Zhongming, DOU Guifang, et al Academy of Military Medical Sciences, Institute of Radiation Medicine, Beijing 100850, China  

Objective To study the binding, degradation and concentration time profiles of 125 I kallidinogenase in plasma after i v injection in rabbits The distribution and excretion of kallidinogenase and its metabolites in urine and bile were also studied in rats Methods Using 125 I kallidinogenase combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid precipitation method Results Determined by hydrolysis of chromogenic substrate (S 2266) of kallidinogenase, demonstrated that the enzymatic activity of 125 I kallidinogenase was similar to that of unlabelled enzyme SHPLC analysis of plasma revealed that plasma protein bound 125 I kallidinogenase and 125 I degradation products were found after intravenous injection of various doses of the agent Terminal half lives of 125 I kallidinogenase protein complex (AUC) after i v 5×10 -3 , 15×10 -3 , and 45×10 -3 pNAu·kg -1 were (1 28±1 31), (2 18±1 08) and (2 03±0 32) h, respectively AUC increased with dose while clearence was similar Maximal percentage of bound serum 125 I kallidinogenase in vitro was (94 3±0 77)% and equilibrium dissociation constant (K d) was 8 9×10 -8 mol·L -1 Levels of acid precipitable radioactivity in different organs were in a decending order: urinary system, the highest blood abundant organs the next and cerebral cortext the lowest (96 9±3 3)% of injected radioactivity was excreted within 2 days and the major route was urinary system Conclusions 125 I kallidinogenase was rapidly bound to plasma protein with high affinity after i v injection The pharmacokinetics of 125 I kallidinogenase protein complex was linear within dosage range studied in rabbits 125 I kallidinogenase was mainly distributed in blood abundant organs, not able to across blood brain barrier and excreted through urine after i v injection in rats

【Key Words】： Kallikrein Rabbits Rats Pharmacokinetics
【CateGory Index】： R96
【DOI】： CNKI:SUN:ZHHY.0.2000-02-019

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