盐酸比格列酮缓释微丸在犬体内的药动学与体内外相关性研究

发布时间：2018-11-22 07:59

【摘要】：目的:研究盐酸比格列酮(PGH)缓释微丸在犬体内的药动学和体内外相关性。方法:将6只Beagle犬随机均分为两组,分别ig给予受试制剂PGH缓释微丸和参比制剂PGH片,给药剂量为0.4 mg/kg,1周后交叉实验。分别于给药前和给药后0.5、1、1.5、2、3、4、5、6、8、10、13、24、36 h取血2 ml制备血浆。采用高效液相色谱法测定其血药浓度,3p97软件计算药动学参数,并考察其体内外相关性。色谱柱为Thermo Hypersil GOLD C18,流动相为甲醇-25 mmol/L乙酸铵水溶液-甲酸(70∶30∶0.2),流速为1.0 ml/min,柱温为30℃,检测波长为240 nm,进样量为20μl。结果:PGH检测质量浓度的线性范围为0.1~3.2μg/ml(r=0.999 7),方法回收率为95.0%~101.7%(RSD为4.56%~6.77%,n=3),提取回收率为67.9%~70.3%(RSD为5.53%~8.72%,n=3)。受试制剂的药-时曲线符合单室模型;受试制剂与参比制剂的tmax分别为(10.59±0.37)、(2.21±0.14)h,t1/2分别为(11.75±0.55)、(6.98±0.39)h,cmax分别为(2.01±0.21)、(2.35±0.33)μg/ml,AUC0-36 h分别为(38.57±5.53)、(33.73±4.31)μg·h/ml;受试制剂相对生物利用度为114.3%;体外释药与体内吸收数据的相关系数r=0.910 3。受试制剂tmax及t1/2较参比制剂明显延长,cmax较参比制剂有所降低。结论:PGH缓释微丸具有缓释特征,体外释药与体内吸收具有相关性。
[Abstract]:Aim: to study the pharmacokinetics and in vitro correlation of biglitazone hydrochloride (PGH) sustained-release pellets in dogs. Methods: six Beagle dogs were randomly divided into two groups. Ig was given PGH sustained-release pellets and reference PGH tablets respectively. The blood samples were collected for 2 ml before and after administration of the drug for 2 ml. High performance liquid chromatography (HPLC) was used to determine the drug concentration. The pharmacokinetic parameters were calculated by 3p97 software and the correlation between in vivo and in vitro was investigated. The chromatographic column was Thermo Hypersil GOLD C18, the mobile phase was methanol-25 mmol/L ammonium acetate aqueous solution (70: 30: 0.2), the flow rate was 1.0 ml/min, the column temperature was 30 鈩，

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