摘要
目的:评价自制磷酸卡维地洛缓释微丸在Beagle犬中的等效性。方法:〗流化床包衣法制备磷酸卡维地洛缓释微丸;试验采用两周期交叉试验设计,将6条Beagle犬,雌雄各半,分为两组,分服试验制剂磷酸卡维地洛或参比制剂磷酸卡维地洛;采用HPLC-FD法比较给药后原研和自研制剂在Beagle犬体内不同时间点的血药浓度。计算药动学参数并根据试验制剂和参比制剂AUC计算相对生物利用度。同时对主要药动学参数进行方差分析、双单侧t检验和[1-2α]置信区间分析,评价试验制剂和参比制剂的生物等效性。结果:磷酸卡维地洛在1~300 ng·mL^(-1)范围内线性关系良好(r=0.999 3),定量下限为1ng·mL^(-1)。提取回收率均高于50%,日内、日间RSD均小于12%,专属性良好,在本实验涉及的条件下样品稳定。磷酸卡维地洛缓释微丸试验制剂和参比制剂主要药动学参数t_(1/2)、t_(max)、C_(max)、AUC_(0-t)、AUC_(0-∞)无明显差异,与参比制剂相比较试验制剂相对生物利用度为(96.8±8.7)%。结论:自研制剂与原研制剂在Beagle犬体内生物等效。
OBJECTIVE To evaluate the bioequivalence of homemade carvedilol phosphate sustained release pellets in Beagle dogs.METHODS A laboratory-scale fluid bed was used to prepare sustained release pellets.Six Beagle dogs were divided into two groups randomly according to a two period crossover test design and were orally given the test or reference preparations of carvedilol phosphate sustained release pellets during the two periods.Plasma concentrations were detected by HPLC-FD and the pharmacokinetic parameters were calculated.According to the AUC,relative bioavailability was calculated.Variance,t test and[1-2α]confidence interval were used to evaluate the bioequivalence of test and reference preparations.RESULTS The assay was liner in the range of the calibration curve for determination of carvedilol phosphate（1-300 ng·mL^（-1））with a correlation coefficient of 0.999 3.The lowest limit of quantification was 1 ng·mL^（-1）.The extraction recovery was higher than50%.The intra-and inter-day RSD values were less than 12%.The stability of this method was satisfactory.The statistical analysis showed that the AUC,t_（1/2）、t_（max） and C_（max）were not significantly different between the test and reference preparations.The relative bioavailability of carvedilol phosphate sustained release pellets was（96.8±8.7）%.CONCLUSION The test preparation is bioequivalent to the reference preparation.
出处
《中国医院药学杂志》
CAS
北大核心
2018年第1期14-17,21,共5页
Chinese Journal of Hospital Pharmacy
关键词
磷酸卡维地洛
缓释微丸
生物等效性
比格犬
药动学
carvedilol phosphate
sustained release pellets
biological equivalence
Beagle dogs
pharmacokinetics
