雷贝拉唑钠肠溶胶囊Beagle犬体内药动学及生物等效性研究

Pharmacokinetics and Bioavailability of Rabeprazole Sodium Enteric-Coated Capsules in Beagle Dogs

目的:建立HPLC-MS测定方法分析Beagle犬血浆中雷贝拉唑的含量,并作不同厂家两种雷贝拉唑钠肠溶胶囊的药动学及生物等效性研究。方法:6只Beagle犬随机分为两组,采用单剂量双周期交叉试验,分别口服给予60 mg雷贝拉唑钠肠溶胶囊受试制剂或参比制剂,给药后不同时间点采血,测定血药浓度,利用DAS3.0软件计算药动学参数,并比较两个厂家生产的制剂的生物等效性。结果:Beagle犬单次给予雷贝拉唑钠肠溶胶囊受试制剂和参比制剂后的tmax分别为(3.57±0.91)h和(3.43±0.87)h,Cmax分别为(539.03±129.13)ng·mL-1和(554.90±135.75)ng·mL-1,t1/2分别为(2.20±0.90)h和(2.09±0.78)h,药时曲线下面积AUC(0→24 h)分别为(1341.40±442.03)ng·h·mL-1和(1319.41±402.29)ng·h·mL-1。结论:结果表明不同厂家的两种雷贝拉唑钠肠溶胶囊具有生物等效性。

Objective：To develop an HPLC-MS method for the determination of rabeprazole sodium in dog plasma and investigate the pharmacokinetics and bioequivalence of rabeprazole sodium enteric-coated capsules.Method：By a two-cycle crossover trial,6 beagle dogs were randomly administrated a single crossover dose of test or reference capsules（60 mg）.The blood concentrations of rabeprazole sodium at the preset time-points were determined by the established HPLC-MS/MS method.The pharmacokinetic parameters were calculated and the bioequivalence of the two preparations were evaluated.Results：The main pharmacokinetic parameters of the test and reference capsules were as follows：tmax,（3.57±0.91）h and（3.43±0.87）h;Cmax,（539.03±129.13）ng·mL^-1 and（554.91±135.75）ng·mL^-1;t1/2,（2.20±0.90）h and（2.09±0.78）h;AUC（0→24）,（1341.40±442.03）ng·h·mL^-1 and（1319.41±402.29）ng·h·mL^-1,respectively.Conclusion：The results indicated that the two kinds of rabeprazole sodium enteric-coated capsules were bioequivalent in beagle dogs.