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目的考察普萘洛尔药物树脂缓释混悬剂在Beagle犬体内的缓释行为及其体内外相关性研究。方法采用双周期交叉试验设计,6只健康Beagle犬口服市售缓释胶囊或自制缓释混悬剂后,用HPLC法测定血药浓度,计算2制剂的药动学参数,进行生物利用度比较,用不同的体外释放量对体内吸收量进行线性拟和。结果自制缓释混悬剂的药动学参数计算结果为AUC_(0-24)(1031±s 63)μg·h·L~(-1),c_(max)(87±4)μg·L~(-1),t_(max)(6.5±1.2)h,市售缓释胶囊的计算结果相应为AUC_(0-24)(989±99)μg·h·L~(-1),c_(max)(85±3)μg·L~(-1),t_(max)(7.2±0.7)h,2制剂的3项药动学参数没有显著差异(P>0.05),自制缓释混悬剂对市售缓释胶囊的平均相对生物利用度为(106±9)%,以0.5mol·L~(-1) NaCl溶液中所得体外溶出数据与体内吸收量相关性较好(r=0.937 7)。结论普萘洛尔药物树脂缓释混悬剂在Beagle犬体内达到明显的缓释效果,与参比制剂相比具生物等效性,可用一定的体外释放条件进行体内行为的预测。
Objective To investigate the sustained-release behavior and in vitro-in vivo correlation of propranolol resin sustained-release suspension in Beagle dogs. Methods A double-cycle crossover design was adopted. Six healthy Beagle dogs were orally administrated with sustained-release capsules or self-made sustained-release suspensions. The plasma concentration was determined by HPLC. The pharmacokinetic parameters of two preparations were calculated and bioavailability was compared , With a different amount of in vitro release of the body to absorb the amount of linear and. Results The pharmacokinetic parameters of the self-made sustained-release suspensions were AUC 0-24 (1031 ± s 63) μg · h · L -1 and c max 87 ± 4 μg · L ~ (-1) and t_ (max) (6.5 ± 1.2) h respectively. The calculated results of commercially available sustained release capsules were AUC 0-24 (989 ± 99) μg · h · L -1, There was no significant difference in the three pharmacokinetic parameters between the two preparations (max 85 ± 3 μg · L -1, t max 7.2 ± 0.7 h, P <0.05) The average relative bioavailability of the suspension to commercially available sustained-release capsules was (106 ± 9)%. The in vitro dissolution data obtained in 0.5mol·L -1 NaCl solution showed good correlation with the in vivo absorption (r = 0.937 7). Conclusion Propranolol drug-resin sustained-release suspensions achieve significant sustained-release effect in Beagle dogs, which is bioequivalent compared with the reference formulation. Some in vitro release conditions can be used to predict in vivo behavior.