盐酸普罗帕酮缓释胶囊在家犬体内的药物动力学考察

Pharmacokinetics and bioavailability of propafenone hydrochloride sustained release capsules in dogs

目的考察家犬口服盐酸普罗帕酮缓释胶囊的药物动力学,分析AUC0-t数据,比较普通片与缓释胶囊的生物利用度。方法家犬6只采用两制剂双周期交叉试验,HPLC法测定盐酸普罗帕酮在家犬血浆内的质量浓度,通过3P87药物动力学程序对两种制剂在家犬体内的动态过程进行拟和。药-时曲线下面积AUC0-t由梯形法求得,ρmax、tmax为实测值。结果盐酸普罗帕酮缓释胶囊和市售普通片在家犬体内过程均符合单隔室模型,其主要的药物动力学参数ρmax、tmax和AUC0-t分别为(1.41±0.13)、(1.92±0.05)mg.L-1,(6.00±1.55)、(1.50±0.45)h,(8.45±0.84)(、7.88±0.98)mg.h.L-1。以普通片为参比制剂,缓释胶囊的生物利用度为(96.4±15.0)%。结论盐酸普罗帕酮缓释胶囊具有明显的缓释特征,主要药物动力学参数发生了变化,生物利用度与市售普通片等效。

Objective To study the pharmacokinetics and bioavailability of propafenone hydrochloride sustained release capsules in dogs. Methods Test and reference formulations were administrated to 6 dogs by double crossing method in two weeks. The concentrations of propafenone hydrochloride in plasma were determined by HPLC. The pharmacokinetic parameters were analyzed by 3P87 program. Results The pharmacokinetics of propafenone hydrochloride sustained release capsules and propafenone hydrochloride tablets in the market fitted to one-compartment model. The pharmacokinetic parameters of sustained release capsules and reference tablets were tmax（6. 00 ± 1.55 ）h and（1.50 ± 0.45）h; ρmax（1. 41 ± 0. 13）mg·L^-1 and （1.92 ± 0.05 ） mg·L^-1 ; AUC0-t （ 8.45 ± 0.84 ） mg·h·L^-1 and （7.88 ± 0.98 ） mg·h·L^-1, respectively. The relative bioavailability of sustained release capsules were（96. 4 ± 15.0）% compared with reference tablets. Conclusions Propafenone hydrochloride sustained release capsules were characterized with sustained-releasing profile, and the main pharmacokinetic parameters of propafenone hydrochloride in sustained release cap- sules were different from the reference tablets. The relative propafenone hydrochloride sustained release capsules were bioequivalent to the tablets in the market.