厄贝沙坦胃滞留渗透泵片的制备及其在犬体内的药动学研究

Study on Preparation and Pharmacokinetics of Irbesartan Intragastric Floating Osmotic Pump Tablets in Dogs

目的:制备厄贝沙坦胃滞留渗透泵片,研究其在犬体内的药动学。方法:采用湿法制粒包衣的方法制备厄贝沙坦胃滞留渗透泵片;6只犬自身交叉给药,分别单剂量灌胃厄贝沙坦片和厄贝沙坦胃滞留渗透泵片150mg。采用高效液相色谱-荧光检测法考察给药前和给药后0.25、0.5、0.75、1、1.5、2、3、4、6、8、12、24、36、48、72h犬血浆中厄贝沙坦浓度,采用DAS统计软件计算药动学参数及相对生物利用度,评价其缓释特性。结果:制得单剂量为150mg的厄贝沙坦胃滞留渗透泵片。厄贝沙坦片和厄贝沙坦胃滞留渗透泵片在犬体内的主要药动学参数:tmax分别为(1.21±0.76)、(5.43±3.79)h,cmax分别为(2.93×104±0.71×104)、(1.87×104±0.45×104)μg/L,t1/2分别为(14.2±4.9)、(17.5±4.7)h,AUC0-72h分别为(6.57×105±1.19×105)、(6.07×105±8.61×104)μg·h/L,胃滞留渗透泵片的相对生物利用度为(92.1±18.5)%;其中tmax、cmax均有明显差异。结论:在犬体内,厄贝沙坦胃滞留渗透泵片具有明显缓释作用。

OBJECTIVE：To prepare Irbesartan intragastric floating osmotic pump tablets（IFOPT）,and to study the pharmacokinetics of irbesartan in dogs.METHODS：Irbesartan IFOPT was prepared by wet granulation coating method.A single oral dose of 150mg Irbesantan tablets and Irbesartan IFOPT were given to 6 dogs in a randomized crossover design.The concentrations of irbesantan in plasma were determined by HPLC-fluorescence before medication and 0.25,0.5,0.75,1,1.5,2,3,4,6,8,12,24,36,48 and 72h after medication.The pharmacokinetic parameters were calculated with DAS statistics software to evaluate sustained-release effect.RESULTS：The main pharmacokinetic parameters of Irbesartan tablet and Irbesartan IFOPT 150 mg were as follows：tmax：（1.21±0.76）h and（5.43±3.79）h;cmax：（2.93×104±0.71×104）μg/L and（1.87×104±0.45×104）μg/L;t1/2：（14.2± 4.9）h and（17.5±4.7）h;AUC0-72h（6.57×105±1.19×105）μg·h/L and（6.07×105±8.61×104）μg·h/L.The relative bioavailability of IFOPT was（92.1±18.5）%.There were significant differences in tmax and cmax.CONCLUSION：Irbesantan IFOPT have good sustained-release effect in dogs.