抗球虫新药AC4在SD大鼠体内的药代动力学研究  

PHARMACOKINETICS OF A NEW COCCIDOISTAT AC4 IN RATS

作　　者：王春梅[1] 林析 张可煜[1] 张丽芳[1] 田玉柱 费陈忠[1] 张晓晓[1] 赵娟[1] 肖遂[1] 王霄旸[1] 王米[1] 郑文丽[1] 薛飞群[1] 

机构地区：[1]中国农业科学院上海兽医研究所,上海200241 [2]齐鲁动物保健品有限公司,济南250100

出　　处：《中国动物传染病学报》2016年第4期64-71,共8页Chinese Journal of Animal Infectious Diseases

基　　金：国家自然科学基金项目(31272607);上海自然科学基金项目(14ZR1449000);公益性行业(农业)科研专项(201303038)

摘　　要：本研究的目的是建立检测SD大鼠血浆内AC4的分析方法,考察高、中、低3个剂量的AC4在SD大鼠体内的药代动力学特征,获得主要的药代动力学参数。采用超高液相色谱法检测SD大鼠血浆内AC4含量,使用乙酸乙酯作为提取溶剂,妥曲珠利亚砜作为内标。研究表明,建立的方法专属性良好,标准曲线定量范围0.08-80μg/mL,线性关系良好;准确度和精密度均能达到检测目的,样品在室温放置8 h或者反复冻融3次后稳定;该方法灵敏、准确,可以用于检测SD大鼠血浆内AC4含量。药时曲线下面积和最大血药浓度存在剂量正相关关系,给药后4-5 h达到最大血药浓度,生物消除半衰期在不同性别、不同剂量组之间存在较大差异,AC4在SD大鼠的药动学存在较为明显的性别差异。本研究结果为AC4后期研究和临床合理应用提供了参考依据。The objective of the present study was to develop a measurement of AC4 within the plasmas of SD rats and examine the pharmacokinetics of AC4 in these animals.In the UPLC-UV method,ethylacetate was used as the extraction solvent and toltrazuril sulphoxide as an internal standard.The limits of detection and quantification were 0.04 and 0.08 μg/mL,respectively.The line arrange of the standard curve was 0.08-80 μg/mL.In addition,the sample was stable after storage for 8 h at room temperature or 3 cycles of freezing and thawing.The method was sensitive,accurate and therefore suitable for detection of AC4 in SD rat plasma samples.In the pharmacokinetic study of AC4 in SD rats,doses of 0.45,0.9 and 4.5 mg / kg · BW were examined in male and female SD rats.The results showed a dose-dependent manner of AUC and Cmax in both male and female SD rats.The AC4 peaked in the plasmas around 4 h post application.There were significant differences of the biological elimination half-life of AC4 between genders and doses.

关 键 词：AC4 SD大鼠 UPLC-UV 药代动力学 

分 类 号：S859.795[农业科学—临床兽医学]