大鼠单次静注和口服赭曲霉毒素A的毒代动力学研究  

Toxicokinetics of mycotoxin ochratoxin A in Sprague-Dawley rats after a single intravenous and oral administration

作　　者：李亚菲 苏佳 万鹏 张彩云 吴维煇 秦华 曾振灵[2] LI Ya-fei;SU Jia;WAN Peng;ZHANG Cai-yun;WU Wei-yun;QIN Hua;ZENG Zhen-ling(Public Monitoring Center for Agro-product,Guangdong Academy of Agricultural Sciences,Guangzhou 510640,China;Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation,South China Agricultural University,Guangzhou 510642,China;Beijing Humanwell Junwei Healthcare Technology Development Co.,Ltd,Beijing 102600,China)

机构地区：[1]广东省农业科学院农产品公共监测中心,广东广州510640 [2]华南农业大学广东省兽药研制与安全评价重点实验室,广东广州510642 [3]北京人福军威医药技术开发有限公司,北京102600

出　　处：《中国兽医科学》2020年第1期99-105,共7页Chinese Veterinary Science

基　　金：广东省自然科学基金-博士启动项目(2016A030310324);广东省兽药研制与安全评价重点实验室运行经费项目(2014B030301067)

摘　　要：旨在考察大鼠单剂量静注和经口染毒赭曲霉毒素A(ochratoxin A,OTA)的血浆毒代动力学特征。选用16只健康雌性SD大鼠,随机分成2组,分别通过单剂量静注(i.v.)和经口(p.o.)染毒OTA(剂量为0.5 mg/kg),血液采样时间点为染毒后第0、0.25、0.5、1、1.5、2、3、4、6、8、12和24小时,之后每24 h采样1次直到720 h。采用高效液相色谱-荧光检测法测定血浆样品OTA的质量浓度,用WinNonlin 5.2.1软件对血浆OTA浓度-时间数据进行非房室模型分析,计算OTA的毒代动力学参数。结果表明,静注染毒:血浆OTA浓度-时间曲线下面积(AUC0→+∞)为(369.25±40.67)μg·m L^-1·h,消除半衰期(t1/2β)为(50.06±5.74) h,表观分布容积(Vd)为(0.10±0.01) L/kg,体清除率(ClB)为(1.39±0.1) m L/(h·kg),平均滞留时间(MRT)为(109.83±7.49) h,稳态分布容积(Vss)为(0.15±0.01) L/kg。经口染毒:达峰时间为(2.38±0.70) h,峰浓度为(3.57±0.13)μg/m L,AUC0→+∞为(172.53±31.30)μg·m Lμ·h,t1/2β为(51.65±3.82) h,Vd/F为(0.22±0.04)L/kg,ClB/F为(3.00±0.50) m L/(h·kg),MRT为(105.36±19.75) h,Vss/F为(0.31±0.04) L/kg。SD大鼠经口染毒OTA的生物利用度为46.72%。经口染毒后,OTA可以被大鼠有效吸收、分布广泛且消除较慢。This experiment was conducted to study the plasma toxicokinetics of ochratoxin A(OTA)after a single intravenous and oral administration in rats.A total of 16 healthy female Sprague-Dawley(SD) rats were randomly allocated into two groups of eight.Animals in the two groups were administered at a single dose of 0.5 mg/kg body weight intravenously(i.v.) and orally(p.o.),respectively.Blood samples were collected by tail vein into heparinized tubes at 0,0.25,0.5,1,1.5,2,3,4,6,8,12,24 h and every 24 h until 720 h after administration.All the samples were analyzed by high performance liquid chromatography equipped with fluorescence detection(HPLC-FLD).The software Win Nonlin 5.2.1 was used to analyze the toxicokinetics data by non-compartmental method.The main toxicokinetic parameters of OTA in female SD rats were presented as follows.After i.v.administration,area under the concentrationtime curve(AUC0→+∞) was(369.25±40.67) μg· m L^-1·h,elimination half-life(t1/2β) was(50.06±5.74) h,apparent volume of distribution(Vd) was(0.10±0.01) L/kg,body clearance(ClB) was(1.39±0.1) L/(h·kg)mean residence time(MRT) was(109.83±7.49) h,apparent volume of distribution at steady state(Vss) was(0.15±0.01) L/kg.After p.o.administration,peak time to peak concentration(tmax) was(2.38±0.70) h,concentration(Cmax) was(3.57±0.13) μg/m L,AUC0→+∞was(172.53±31.30) μg·m L^-1·h,t1/2β was(51.65±3.82) h,Vd/F was(0.22±0.04)L/kg,ClB/F was(3.00±0.50) m L/(h·kg),MRT was(105.36±19.75) h,Vss/F was(0.31±0.04) L/kg.The oral bioavailability of OTA in SD rats was 46.72%.These results indicated that OTA was effectively absorbed through oral administration,widely distributed and slowly eliminated in female SD rats.

关 键 词：赭曲霉毒素A 大鼠 毒代动力学 

分 类 号：S852.8[农业科学—基础兽医学]