盐酸胺碘酮包衣脉冲片在犬体内的药动学研究

目的：建立测定盐酸胺碘酮包衣脉冲片在家犬体内血药浓度的方法,研究其药动学特征。方法：将家犬随机均分成盐酸胺碘酮包衣脉冲片组和普通片组,每日灌服200mg,1周后交叉实验,采用高效液相色谱法测定给药后24h内盐酸胺碘酮在2组家犬体内的血药浓度,并计算比较2组的药动学参数。色谱柱为Agilent C18,流动相为2%三乙胺（用磷酸调pH值至4.8）-乙腈（30：70）,柱温为25℃,检测波长为242nm。结果：盐酸胺碘酮检测浓度的线性范围为5～200μg·mL-1（r=0.9999）,提取回收率为91.62%～95.82%,RSD为1.83%～3.68%;盐酸胺碘酮在包衣脉冲片组和普通片组家犬体内的药动学参数分别为：t1/2为（17±1.68）、（18±2.16）h,tlag为（4.42±0.3）、（0.2±0.05）h,AUC0～24h为（298.4±32.5）、（278.4±24.8）μg·h·mL-1,cmax为（23.56±2.12）、（24.89±1.56）μg·mL-1,其中tlag有明显差异（P〈0.01）,而t1/2、cmax、AUC0～24h等无明显差异（P〉0.05）。结论：盐酸胺碘酮包衣脉冲片具有缓释作用,体内实验满足脉冲释药时滞效果。

Pharmacokinetic Study of Amiodarone Hydrocholride Coated Pulsatile-release Tablets in Dogs in Vivo

OBJECTIVE：To establish the method for the determination of plasma concentration of Amiodarone hydrocholride coated pulsatile-release tablets in dogs,and to study the pharmacokinetic characteristics.METHODS：The dogs were randomly assigned into Amiodarone hydrocholride coated pulsatile-release tablets group and conventional tablets group.They were given relevant medicines 200 mg and crossed 1 week later.Plasma concentrations of amiodarone hydrocholride in dogs of 2 groups within 24 h were quantified by HPLC.The pharmacokinetic parameters were calculated and compared.Agilent C18 column was used with mobile phase consisted of 2% triethylamine（pH adjusted to 4.8 with phosphoric acid）-acetonitribe（30：70）.The column temperature was 25 ℃ and detection wavelength was set at 242 nm.RESULTS：The linear range of amiodarone hydrocholride was 5～200 μg·mL-1（r=0.999 9）with recovery of 91.62%～95.82%（RSD=1.83%～3.68%）;the pharmacokinetic parameters of amiodarone hydrocholride in coated pulsatile-release tablets group vs.conventional tablets group were as follows：t 1/2：（17±1.68）、（18±2.16） h,t lag：（4.42±0.3）、（0.2±0.05）h,AUC 0～24h：（298.4±32.5）、（278.4±24.8）μg·h·mL-1,c max：（23.56±2.12）、（24.89±1.56）μg·mL-1.There was significant difference in t lag（P0.01）but no significant difference in t 1/2,c max and AUC 0～24 h（P0.05）.CONCLUSIONS：Amiodarone hydrocholride coated pulsatile-release tablets show sustained-release effect,and achieve the goal of pulsatile-release lag time.