【摘要】：目的:研究鹽酸比格列酮(PGH)緩釋微丸在犬體內(nèi)的藥動學和體內(nèi)外相關(guān)性。方法:將6只Beagle犬隨機均分為兩組,分別ig給予受試制劑PGH緩釋微丸和參比制劑PGH片,給藥劑量為0.4 mg/kg,1周后交叉實驗。分別于給藥前和給藥后0.5、1、1.5、2、3、4、5、6、8、10、13、24、36 h取血2 ml制備血漿。采用高效液相色譜法測定其血藥濃度,3p97軟件計算藥動學參數(shù),并考察其體內(nèi)外相關(guān)性。色譜柱為Thermo Hypersil GOLD C18,流動相為甲醇-25 mmol/L乙酸銨水溶液-甲酸(70∶30∶0.2),流速為1.0 ml/min,柱溫為30℃,檢測波長為240 nm,進樣量為20μl。結(jié)果:PGH檢測質(zhì)量濃度的線性范圍為0.1~3.2μg/ml(r=0.999 7),方法回收率為95.0%~101.7%(RSD為4.56%~6.77%,n=3),提取回收率為67.9%~70.3%(RSD為5.53%~8.72%,n=3)。受試制劑的藥-時曲線符合單室模型;受試制劑與參比制劑的tmax分別為(10.59±0.37)、(2.21±0.14)h,t1/2分別為(11.75±0.55)、(6.98±0.39)h,cmax分別為(2.01±0.21)、(2.35±0.33)μg/ml,AUC0-36 h分別為(38.57±5.53)、(33.73±4.31)μg·h/ml;受試制劑相對生物利用度為114.3%;體外釋藥與體內(nèi)吸收數(shù)據(jù)的相關(guān)系數(shù)r=0.910 3。受試制劑tmax及t1/2較參比制劑明顯延長,cmax較參比制劑有所降低。結(jié)論:PGH緩釋微丸具有緩釋特征,體外釋藥與體內(nèi)吸收具有相關(guān)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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