2种头孢氨苄片在比格犬体内的药代动力学及生物等效性试验  

Pharmacokinetics and Bioequivalence of Two Cephalexin Formulations in Beagle Dogs

作　　者：杨宇欣 赵富华[3] 刘羽 邱基程 曹玉颖 张璐[1,2] 白如念 王建中 曹兴元 YANG Yuxin;ZHAO Fuhua;LIU Yu;QIU Jicheng;CAO Yuying;ZHANG Lu;BAI Runian;WANG Jianzhong;CAO Xingyuan(College of Veterinary Medicine,China Agricultural University,Beijing 100193,China;Reference Laboratory for the Test of Veterinary Drug Residues,Beijing 100193,China;China Institute of Veterinary Drug Control,Beijing 100081, China;Beijing Center for Animal Diseases Prevention and Control,Beijing 100013,China;College of Veterinary Medicine,Shanxi Agricultural University,Taigu 030801,China)

机构地区：[1]中国农业大学动物医学院,北京100193 [2]国家兽药残留基准实验室,北京100193 [3]中国兽医药品监察所,北京100081 [4]北京市动物疫病预防控制中心,北京100013 [5]山西农业大学动物医学学院,太谷030801

出　　处：《中国畜牧兽医》2022年第1期386-394,共9页China Animal Husbandry & Veterinary Medicine

基　　金：抗菌药物代谢转归及环境微生态风险评估(2018YFD0500301)。

摘　　要：【目的】研究头孢氨苄片受试制剂和参比制剂在比格犬体内的生物等效性。【方法】采用双周期和双序列交叉设计,将22只健康比格犬随机分成2组,按30 mg/kg BW分别单剂量口服头孢氨苄片受试制剂Trolevis300和参比制剂Rilexine300,于给药前(0 h)和给药后0.5、1、1.5、2、2.5、3、4、6、8、12、17和24 h从臂头静脉采血。对超高效液相色谱串联质谱(UPLC-MS/MS)方法进行特异性、线性、检测限、准确度、精密度、稳定性等方法学考察。利用建立好的UPLC-MS/MS方法测定血浆中的药物浓度,并用WinNonlin^(TM) 8.1软件对药代动力学参数进行分析计算。【结果】方法学结果显示,在100~5000 ng/mL浓度范围内相关性良好,相关系数(R^(2))≥0.99,标准曲线方程为y=10.6828x-176.481;高、中、低3个浓度的相对回收率平均值分别为105.63%、104.35%和102.40%;日内和日间变异系数均<15%;检测限为50 ng/mL,定量限为100 ng/mL。药代动力学结果显示,参比制剂组和受试制剂组药代动力学参数如下:T_(max)分别为(1.77±0.55)和(2.70±4.68)h;C_(max)分别为(28.09±5.09)和(26.82±7.94)μg/mL;T_(1/2)分别为(3.39±1.43)和(3.12±1.05)h;AUC_(0-t)分别为(121.81±25.80)和(116.34±36.30)μg·h/mL。受试制剂与参比制剂药时曲线相似,且受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)几何均数的比值分别为99.51%、99.27%和99.30%,其90%CI均在80.00%~125.00%之间。【结论】本试验建立的UPLC-MS/MS方法准确、可靠,可用于头孢氨苄的浓度测定,且头孢氨苄受试制剂与参比制剂是等效的,临床上均可用于相关疾病的治疗。【Objective】The purpose of the experiment was to study the bioequivalence of cephalexin test and reference formulations in Beagle dogs.【Method】Twenty-two Beagle dogs were randomly allocated to two equal-sized treatment groups in a randomized dual-cycle and dual-sequence cross-over design.The test(Trolevis300)and the reference(Rilexine300)formulations were orally administered in a single dose of 30 mg/kg BW.Blood samples were collected from brachiocephalic vein at 0,0.5,1,1.5,2,2.5,3,4,6,8,12,17 and 24 h after administration.The specificity,linearity,detection limit,accuracy,precision,and stability of UPLC-MS/MS method were investigated.The concentration of cephalexin in plasma was determined by UPLC-MS/MS.The pharmacokinetic parameters were analyzed and calculated with WinNonlin^(TM) 8.1.【Result】The methodological results showed good correlation over the concentration range of 100-5000 ng/mL with a correlation coefficient(R^(2))≥0.99 and a standard curve equation of y=10.6828x-176.481.Relative recoveries were 105.63%,104.35%and 102.40%for high,medium and low concentrations.Coefficient variations of intra-day and inter-day were all less than 15%,and the limit of detection and the limit of quantification were 50 and 100 ng/mL,respectively.The pharmacokinetic parameters of the two groups were as follows:T_(max) were(1.77±0.55)and(2.70+4.68)h,C_(max) were(28.09±5.09)and(26.82±7.94)μg/mL;T_(1/2) were(3.39±1.43)and(3.12±1.05)h;AUC_(0-t) were(121.81±25.80)and(116.34±36.30)μg·h/mL.The plasma profiles of cephalexin following the administration of both formulations were similar.And the ratio of the average C_(max),AUC_(0-t) and AUC_(0-∞) of the test/reference preparation were 99.51%,99.27%and 99.30%respectively,the 90%CI all fell between 80.00%-125.00%.【Conclusion】The UPLC-MS/MS method established in this experiment was accurate and reliable,and could be used to determine the concentration of cephalexin.The two formulations were bioequivalent for cephalexin,and could be used clinically fo

关 键 词：药代动力学 生物等效性 比格犬 头孢氨苄片 超高效液相色谱串联质谱 

分 类 号：S89.796[农业科学—特种经济动物饲养]