普萘洛尔药物树脂缓释混悬剂在Beagle犬体内的药动学

Pharmacokinetic of propranolol resinate sustained-release suspension in Beagle dogs

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。

AIM To determine the pharmacokinetics of propranolol-resinate sustained-release suspension and the referenced sustained-release capsule in Beagle dogs and study the correlation between absorption in vivo and release in vitro for the sustained-release suspension. METHODS The relative bioavailabilities of the two preparations were evaluated in six Beagle dogs according to a randomized two way crossover design. The pharmacokinetics parameters of propranolol sustained-release suspension and referenced sustained-release capsule concentrations were determined by HPLC method. The plasma drug in vitro and absorption in vivo were fitted. RESULTS Pharmacokinetics parameters of two preparations were as follow： A UC0-24 （1 031 ± s 63） μg· h·L^-1 and （989 ± 99） μg· h·L^-1, cmax （87 ± 4） μg·L^-1 and （85 ± 3） μg·L^-1, tmax （6.5 ± 1.2） h and （7.2 ± 0.7） h respectively, and there were no significant differences between the two preparations （P 〉 0.05）. The relative bioavailability of the sustained-release suspension was （106 ± 9） %. Obvious correlation （r = 0.937 7） in vivo and in vitro was observed when the drug released from the suspension in 0.5 mol·L^-1 NaCl solution. CONCLUSION Propranolol-resinate sustained-release suspension is able to maintain a sustained release in Beagle dogs for 24 h. The two preparations are bioequivalent, and the drug absorption characteristic in vivo could be predicted according to certain release conditions in vitro.