左乙拉西坦缓释片在Beagle犬中的生物等效性研究  

Bioequivalence of levetiracetam extended-release tablets in Beagle dogs

作　　者：陈仁海[1] 黄晓玲[1] 邓轶方[1] 刘全海[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海200437

出　　处：《药学实践杂志》2015年第1期32-35,共4页Journal of Pharmaceutical Practice

摘　　要：目的以Beagle犬为模型考察自制左乙拉西坦缓释片与参比缓释片(Keppra XR)在动物体内的生物等效性。方法 Beagle犬分别单剂量口服自制缓释片与参比制剂1 000mg,采用LC-MS/MS方法测定犬血浆中左乙拉西坦的浓度,通过药代动力学计算软件WinNonlin 5.2以非房室模型分别计算左乙拉西坦的药代动力学参数。结果自制缓释片与市售参比缓释片单剂量口服后,左乙拉西坦的达峰时间tmax分为1.67h和3.0h;峰浓度Cmax分别为89.50μg/ml和71.18μg/ml;消除半衰期t1/2分别为3.68h和3.50h;药时曲线下面积AUC(0-48)分别为826.57μg·h/ml和757.84μg·h/ml;药时曲线下面积AUC(0-∞)分别为826.68μg·h/ml和757.93μg·h/ml。与参比缓释片相比,自制左乙拉西坦缓释片的相对生物利用度为109.07%。结论初步判定两种制剂在犬体内具有类似的药代动力学特征和生物等效性。Objective To study the bioequivalence of two kinds of levetiracetam extendedrelease tables including the reference product of Keppra XR in Beagle dogs .Methods Dogs were administrated orally with single dose of levetiracetam tablets （1 000 mg） .The concentration of levetiracetam in dog plasma was detected by LCMS/MS .All parameters of pharmacokinetics were performed by WinNonlin 5 .2 software .Results Main pharmacokinetic parameters of test and reference tablets were as follow ：tmax were 1.67 h and 3 .0 h ,Cmax were 89 .50 μg/ml and 71 .18 μg/ml ,t1/2 were 3 .68 h and 3 .50 h ,AUC（048） were 826 .57 μg·h/ml and 757 .84 μg·h/ml ,AUC（0∞ ）were 826 .68 μg·h/ml and 757 .93 μg·h/ml .The relative bioavailability of test tablets was 109 .07% to reference products of Keppra XR .Conclusion Therefore ,the two kinds of levetiracetam extendedrelease tablets were bioequivalent in Beagle dogs .

关 键 词：左乙拉西坦 缓释片 生物等效性 

分 类 号：R945[医药卫生—微生物与生化药学]