吲达帕胺控释片在Beagle犬体内的药动学和相对生物利用度

Pharmacokinetics and relative bioavailability of indapamide controlled release tablets in Beagle dogs

目的：研究健康Beagle犬口服吲达帕胺控释片的药动学和相对生物利用度。方法：采用两制剂、双周期交叉试验设计,用HPLC-MS法测定6只健康Beagle犬单次口服1.5 mg受试制剂（吲达帕胺控释片）和参比制剂（市售吲达帕胺缓释片）后血浆中吲达帕胺浓度,并绘制血药浓度-时间曲线;用统计分析软件计算药动学参数,进而计算相对生物利用度。结果：受试犬服用受试制剂和参比制剂后药时曲线相似,血浆中吲达帕胺的t1/2分别为（11.71±1.69）和（11.87±1.72）h;Cmax分别为（87.17±22.03）和（87.64±24.24）μg·L^-1;Tmax分别为（6.67±0.52）和（6.83±0.75）h;AUC0-48 h分别为（1 200.31±577.16）和（1 162.53±463.85）μg·h·L^-1;AUC0~∞分别为（1 276.73±619.22）和（1 250.20±507.63）μg·h·L^-1。以AUC0~48 h计算,受试制剂的相对生物利用度F为（101.0±17.7）%。结论：吲达帕胺控释片具有与市售缓释片相似的缓释效果,主要药动学参数无显著差异,两个制剂生物利用度接近。

Objective：To study the pharmacokinetics and relative bioavailability of indapamide controlled release tablets in healthy Beagle dogs.Methods：Indapamide controlled release tablets（test product） and indapamide sustained release tablets（reference product） were given orally to six healthy Beagle dogs by a two-crossover design.Indapamide concentrations in plasma were determined by HPLC-MS and the plasma concentration-time curves were plotted.The pharmacokinetic parameters and relative bioavailability were calculated and evaluated using statistic computer program.Results：The concentration-time curve of indapamide controlled release tablets was similar to that of indapamide sustained release tablets,and their t1/2 were（11.71±1.69） and（11.87±1.72） h,Cmax were（87.17±22.03） and（87.64±24.24） μg·L^-1,Tmax were（6.67±0.52） and（6.83±0.75） h,AUC0~48 h were（1 200.31±577.16） and（1 162.53±463.85） μg·h·L^-1,AUC0~∞ were（1 276.73±619.22） and（1 250.20±507.63） μg·h·L^-1,respectively.According to AUC0~48 h,the relative bioavailability of indapamide controlled release tablets was（101.0±17.7）%.Conclusion：Compared with the sustained release tablets,indapamide controlled release tablets have similar pharmacokinetic profile and bioavailability.