嘧菌酯在大鼠体内的毒物代谢动力学研究  

Study on toxicokinetics and tissue distribution of azoxystrobin in rats

作　　者：程桂红[1] 张康[2] 庄宛[3] 李龙[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院卫生毒理学系教育部环境与健康重点实验室,湖北武汉430030 [2]柳州市疾病预防控制中心 [3]厦门出入境检验检疫局检验检疫技术中心

出　　处：《毒理学杂志》2013年第5期341-344,共4页Journal of Toxicology

摘　　要：目的探讨单次灌胃嘧菌酯原药后,其在大鼠体内的毒代动力学过程、组织分布情况和粪尿排泄情况。方法以2000 mg/kg剂量给SD大鼠灌胃染毒,于给药后5、15和30 min,1、2、4、8、12和24 h采集血液样本;2、8、24、48和96 h后采集组织样本;收集染毒后1、2、3和4 d的粪尿样本,应用高效液相色谱法测定各样本中嘧菌酯的含量,用DAS 3.0软件计算毒代动力学参数。结果嘧菌酯染毒大鼠后,其血浆中的最大浓度为(1.83±0.72)μg/L;分布半衰期为(0.56±0.085)h;消除半衰期为(13.15±4.25)h;浓度曲线下面积为(41.42±8.73)μg/L·h;消除速率为(45299±5178)L/h/kg;表观分布容积为(823907±201696)L/kg。给药后在心、肝、脾、肺、肾、脑、睾丸、肌肉和脂肪组织中均可检测到嘧菌酯原药,且其含量随时间呈逐渐下降趋势。96 h内嘧菌酯0.32‰由尿排出,70.3%由粪便排出。结论嘧菌酯在大鼠体内血浓-时间的经时变化过程符合一级吸收二室开放模型;其毒代动力学特点是:吸收较快,给药后经1 h血浓度即达到峰值;分布范围广,可全身分布,但在被测的组织器官中未见有蓄积作用;排泄快,给药4 d后已基本从体内排出,主要是以未经代谢的原型直接随粪便排泄。Objective To study the toxicokinetics, tissue distribution and excretion of Azoxystrobin in SD rats. Methods After SD rats were exposed at the dose of 2000 mg/kg Azoxystrobin, blood samples were collected at different time intervals： 5, 15 and 30 min, 1, 2, 4, 8, 12 and 24 h; tissue samples were collected at 2, 8, 24, 48 and 96 h; urine and stool samples were collected each day for 4 days. Then HPLC method was used to determine the concentration of Azoxystrobin and the parameters were calculated by DAS 3.0. Results The main parameters of male rats： C （1.83 ±0.72） txg/L; t1/2a, （0.56＋0.085） h; t1/2β, （13. 15±4.25） h; AUC（0-1）, （41.42 ±8.73） μg/L.h; CL/F, （45299 ±5178） L/h/kg; V1/F, （823907 ±201696） L/kg. Azoxystrobin could be detected in heart, liver, spleen, lung and some other organs after exposure, and its content decreased gradually with time. The excretion rates of Azoxystrobin by urine and stool were 0. 32‰ and 70.3% , respectively. Conclusion The results show that the Serum drug-time curve of Azoxystrobin is consistent with first-order kinetics and two-compartment model. The characteristics of toxicokinetics： the absorption of Azoxystrobin is rather rapid that the peak blood concentration occurred at 1 h later after administration. Besides, the distribution is wide and it can be detected systemically, but without accumulative effects detected in the tissues. We also find that the excretion of Azoxystrobin is rather fast, the drug is mainly eliminated directly by stool without being metabolized, and Azoxystrobin is eliminated from the body basically within 4 days.

关 键 词：嘧菌酯 高效液相色谱 毒物代谢动力学 分布 

分 类 号：R114[医药卫生—卫生毒理学]