重组猪干扰素α1冻干粉针剂在猪体内的药代动力学研究  

Pharmacokinetics of recombinant porcine interferon alpha 1 lyophilized powder for injection in pigs

作　　者：赵俊[1,2,3] 俞海洋[1,2] 王兴满[1,2,3] 李京培[1,2,3] 胡涛[1,2] 胡勇[1,2] 苏世云[1,2] 李超[2] 鲁兴生 徐敬东 王明丽[1,2,3] 

机构地区：[1]安徽医科大学微生物学教研室,安徽合肥230032 [2]安徽医科大学中央与地方共建生物医学工程实验室,安徽合肥230032 [3]安徽九川生物科技有限公司,安徽芜湖241000

出　　处：《中国预防兽医学报》2013年第9期756-759,共4页Chinese Journal of Preventive Veterinary Medicine

基　　金：安徽高校省级自然科学研究重大项目(KJ2012ZD08);安徽高校省级自然科学研究项目(KJ2012Z162)

摘　　要：为研究重组猪干扰素α1(rPoIFN-α1)冻干粉针剂在猪体内的药代动力学特征,本研究将实验猪随机分为3组:分别静脉、肌肉和皮下注射rPoIFN-α1 1.0×107IU,每组设立对照组,于注射后间隔不同时间采血,采用细胞病变抑制法测定其血清样品中rPoIFN-α1的效价。结果表明,肌肉注射组和皮下注射组药动学特征符合一室开放模型,呈一级动力学消除,血药峰时间(Tmax)分别为2.872±0.314 h和4.000±0.539 h,消除半衰期(T1/2)分别为6.236±0.551 h和6.644±0.751 h,血药峰浓度(Cmax)分别为3.980±2.875×104IU/L和1.080±0.986×104IU/L。静脉注射组符合二室开放模型,呈一级动力学消除,分布半衰期(T1/2α)为0.136±0.021 h,消除半衰期(T1/2β)为5.195±0.351 h,Cmax值为6.380±0.546×104IU/L。rPoIFN-α1静脉、肌肉和皮下注射组清除率分别为0.930±0.132 L/h、0.677±0.228 L/h和0.879±0.210 L/h。与静脉注射组相比,肌肉注射组的生物利用度为47.82%,皮下注射组的生物利用度为35.09%。本实验结果提示这3种rPoIFN-α1的注射方法在猪体内吸收、消除较快,具有线性动力学特征。rPoIFN-α1肌肉注射给药的生物利用度高于皮下注射组,消除半衰期比静脉注射组延长,可以作为替代静脉注射的一种方便和安全给药途径。To investigate pharmacokinetics of the recombinant porcine interferon alpha1 （rPoIFN-α1） in pigs, sixty-five day-old Landrace pigs were administered with the rPoIFN-α1 （5 pigs in each group） via intravenous, intramuscular or subcutaneous injection, respectively, and the bleed was collected at different time points post injection to detect the titer of rPoIFN-α1 by cytopathic effect inhibition assay. The results indicated the pharmacokinetic models in the rPoIFN-α1 intramuscular injection group and the subcutaneous injection group were consistent with one-compartment open model and featured first-order elimination kinetics simultaneously, and the time of maximum serum concentration （Tmax） were 2.872±0.314 h and 4.000±0.539 h, the elimination half-life （T1/2） were 6.236±0.551 h and 6.644±0.751 h, the maximum serum concentration （Cmax） were 3.980±2.875×104 IU/L and 1.080±0.986×104 IU/L, respectively. The pharmacokinetic in rPoIFN-α1 intravenous injection group was two-compartment model and first-order elimination kinetics with T 1/2α of 0.136±0.021h and T1/2β of 5.195±0.351h. The clearance rate of rPoIFN-α1 in the intravenous group, the intramuscular group and the subcutaneous group was 0.930±0.132 L/h, 0.677±0.228 L/h, and 0.879±0.210 L/h, respectively. In addition, compared with the intravenous group, the bioavailability of rPoIFN-α1 in the intramuscular group was 47.82% and 35.09% in the subcutaneous group. In conclusion, the rPoIFN-α1 was absorbed and eliminated rapidly in the pigs with linear dynamic characteristics via any of the 3 injections. Furthermore, the bioavailability in the intramuscular injection group was higher than that in the subcutaneous group, and the half-life was longer than that in the intravenous group, which could be used as a safe alternative to intravenous route of administration.

关 键 词：重组猪干扰素α1 药代动力学 细胞病变抑制法 

分 类 号：S852.4[农业科学—基础兽医学]