马来酸氟吡汀缓释片在Beagle犬体内的药动学和生物等效性研究  

Pharmacokinetics and bioequivalence of sustained-release flupirtine maleate tablets in Beagle dogs

作　　者：刘秀美[1] 王凌[1] 张颖[2] 蒋学华[1] 

机构地区：[1]四川大学华西药学院,成都610041 [2]四川抗菌素工业研究所,成都610052

出　　处：《药物分析杂志》2012年第10期1731-1735,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立测定Beagle犬血浆中马来酸氟吡汀浓度的高效液相色谱-荧光检测方法,研究马来酸氟吡汀缓释片在Bea-gle犬体内单剂量和多剂量的药动学和生物等效性。方法:以替米沙坦为内标,血浆样品加二氯甲烷萃取,Diamonsil C18为色谱柱,0.005 mol·L-1磷酸氢二钠缓冲液(pH=6.7)-甲醇-乙腈(42∶14.5∶43.5)为流动相,流速为1.0 mL·min-1,进样量10μL,荧光检测波长λex=320 nm,λem=370 nm。采用随机双交叉自身对照试验设计,6只Beagle犬口服单剂量、多剂量马来酸氟吡汀缓释片参比制剂、受试制剂后测定血药浓度,计算药动学参数,评价两制剂的等效性。结果:马来酸氟吡汀的浓度在0.06～15.00μg·mL-1范围内线性关系良好(r=9984),准确度和精密度符合生物样品分析要求;单剂量给药后,参比制剂和受试制剂主要的药动学参数:t1/2分别为(6.97±3.71),(6.39±2.29)h;Cmax分别为(3.83±0.73),(3.81±1.13)μg·mL-1;Tmax分别为(3.17±0.42),(3.67±0.52)h;AUC0→48分别为(27.23±6.31),(27.17±9.33)μg.h.mL-1;AUC0→∞分别为(28.44±7.47),(28.04±9.37)μg.h.mL-1。多剂量给药后,参比制剂和受试制剂主要药动学参数:t1/2分别为(6.50±2.09),(7.94±1.70)h;Tmax分别为(2.08±0.80),(1.83±0.26)h;Csmsax分别为(4.89±0.76),(5.14±0.65)μg·mL-1,Csmsin分别为(0.23±0.19),(0.38±0.22)μg·mL-1;AUCss分别为(29.00±8.32),(30.58±4.33)μg.h.mL-1。结论:本测定方法可用于马来酸氟吡汀Beagle犬药动学研究,且两制剂在Beagle犬体内具有生物等效性。Objective：To establish an HPLC method for determination of flupirtine maleate in dog plasma with fluorescence detection,and evaluate the pharmacokinetics and bioequivalence of flupirtine maleate sustained-release tablets after single or multiple oral dose administration in dogs.Methods：Telmisartan was used as an internal standard,the plasma samples were extracted by dichloromethane.The analytes were separated on a C18column.The mobile phase consisted of disodium phosphate buffer（pH=6.7,0.005 mol·L-1）-methanol-acetonitrile（42∶ 14.5∶ 43.5） with a flow rate of 1.0 mL·min-1.The injection volume was 10 μL.The fluorescence detector were set at λex=320 nm,λem=370 nm.In accordance with randomized two-period self crossover study,six dogs were given single or multiple oral doses of the test preparation and reference preparation,then the concentration of flupirtine maleate in plasma were determined,the pharmacokinetic parameters were calculated and the bioequivalence of the two preparations were evaluated.Results：The linear range of flupirtine maleate in dogs plasma was 0.06-15.00 μg·mL-1.The extraction recovery,accuracy and the precisions of intra-day and inter-day also were qualified.After a single dose administration of the test preparation and reference preparation,the pharmacokinetic parameters were as follow： T1/2 were（6.97±3.71） vs（6.39±229） h;Cmax were（3.83±0.73） vs（3.81±1.13） μg·mL-1;Tmax were（3.17±0.42） vs（3.67±0.52） h;AUC0~48 were（27.23±6.32） vs（27.17±9.33） μg·h·mL-1;AUC0~∞were（28.44±7.47） vs（27.17±9.33） μg·h·mL-1;After a multiple oral administration of the test preparation or reference preparation,the pharmacokinetic parameters were as follow：t1/2were（6.50±2.09） vs（7.94±1.70） h;Tmax were（2.08±0.80） vs（1.83±0.26） h;Cssmax were（4.89±0.76） vs（5.14±0.65） μg·mL-1;Cssmin were（0.23±0.19） vs（0.38±0.22） μg·mL-1;AUCss were（29.00±8.32） vs（30.56±4.33） μg·h·mL-1.Conclusion：The me

关 键 词：马来酸氟吡汀 高效液相色谱法 荧光检测 单剂量给药 多剂量给药 生物等效性 血药浓度 动物血浆 替米沙坦内标 

分 类 号：R917[医药卫生—药物分析学]