重组水蛭素在大鼠体内的药动学研究  

Pharmacokinetics of recombinant hirudin in rats in vivo

作　　者：黄玉荣[1] 李全胜[1] 刘昌孝[1] 

机构地区：[1]天津药物研究院天津药代动力学省部共建重点实验室,天津300193

出　　处：《中草药》2005年第9期1352-1356,共5页Chinese Traditional and Herbal Drugs

基　　金：国家"863"项目资助(2003AA2Z347D)

摘　　要：目的研究重组水蛭素iv给药在大鼠体内的药动学。方法采用125-标记的放射性同位素法(RA法)、三氯醋酸沉淀结合放射性检测法(TCA-RA法)研究重组水蛭素iv给药在大鼠体内的药动学。结果大鼠iv0.5、1.0和2.0mg/kg重组水蛭素,以RA法检测,该药的消除半衰期(t1/2ke)分别为162.8、147.5和172.8min,AUC分别为264.9、429.9和1112.9(μg·min)/mL;以TCA-RA法检测,该药的t1/2ke分别为100、101和107min,AUC分别为160.7、327.7和551.3(μg·min)/mL。两种方法所得结果均证明AUC与剂量呈正相关,相关系数均大于0.99。大鼠iv重组水蛭素1.0mg/kg后用RA法和TCA-RA法测定不同组织的药物质量浓度,在各时间点以肾脏含药量显著高于其他组织,肺、胃、脾、心、肝、性腺等组织次之,脑、脂肪最少。大鼠iv重组水蛭素1.0mg/kg后,用RA法测定不同时间段内尿、粪的放射性总量,在96h内70.16%放射性从尿中回收,1.35%从粪中回收到,24h内胆汁排泄量为3.46%。结论RA法和TCA-RA法测得重组水蛭素在大鼠体内的药动学结果不同,但整体趋势一致;重组水蛭素主要由尿排泄。Objective To investigate the pharmacokinetics of recombinant hirudin （r-hirudin） after iv administration in rats. Methods Two methods, total radioisotope assay with ^125Ⅰ-labeled （RA）, the radioactivity assay after sample deposited with trichloroacetic acid （TCA-RA）, were used to detect r-hirudin after iv administration in rats. Results Rats were given 0.5, 1.0, and 2.0 mg/kg r-hirudin by iv. The pharmacokinetic parameters determined by RA method were as follows ： the elimination half-life t1/2ke, were 162. 8, 147. 5, and 172. 8 min, AUC were 264. 9, 429. 9, and 1 112. 9 （μg· min）/mL. The pharmacokinetic parameters determined by TCA-RA method were as follow： t1/2ke were 100, 101, and 107 min, AUC were 160.7, 327.7, and 551.3 （μg · min）/mL AUC were correlated with doses positively for the two methods （r〉0. 99）. After iv ^125Ⅰ-labeled r-hirudin （1.0 mg/kg） administration, the rank order ofaccumulation of ^125Ⅰ-radiolabeled in the major organs was kidney〉lung〉stomach〉spleen〉heart〉liver〉genital gland）brain and fatty. The accumulation excretion ratios within 96 h were 70. 16% in urine andonly 1.35% in feces after iv administration in rats, while within 24 h was 3. 46% in bile. Conclusion Theresults of pharmacokinetics of novel r-hirudin in rats given by iv determined by RA are different from thosedetermined by TCA-RA, but the trends indicated by the two methods are the same; urine excretion is themajor excretion pathway.

关 键 词：重组水蛭素 放射性 药动学 

分 类 号：R285.61[医药卫生—中药学]