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采用反溶剂法制备妥曲珠利微晶体,利用显微镜观察妥曲珠利微晶体与妥曲珠利原药显微特征差异,并在25℃条件下测定两者体外溶出速率差异。将12只家兔随机分为2组,每组6只,分别按药物剂量10mg/kg灌胃,单剂量给药,采用HPLC检测血药浓度;用DAS2.0药代动力学程序计算药代动力学参数。结果显示,成功制备了妥曲珠利微晶体,微晶体与原药的显微特征差异明显,体外溶出速率明显加快;家兔单剂量灌胃妥曲珠利和微晶体后,主要药动学参数Cmax分别为(8.925±0.360)mg/L和(12.510±0.525)mg/L,tmax均为24h,AUC(0-∞)分别为(411.605±20.918)mg/(L·h)和(578.650±11.664)mg/(L·h),相对生物利用度为140.6%,药时数据符合一级吸收二室模型。结果表明,HPLC法适用于妥曲珠利血浆浓度的测定;妥曲珠利微晶体与妥曲珠利原药相比,体内吸收速率和吸收程度有较大的提高。
Toltrazuril microcrystals were prepared by antisolvent method. The microscopic characteristics of the Toltrazuril microcrystals and Tropetaidil were observed by microscopy. The difference of dissolution rates in vitro between the two samples was determined at 25 ℃. Twelve rabbits were randomly divided into 2 groups with 6 rats in each group. The rabbits were given gavage at a dose of 10 mg / kg and single dose respectively. The blood concentration was measured by HPLC. The pharmacokinetics of DAS2.0 was used to calculate the pharmacokinetics Kinetic parameters. The results showed that Toltrazuril micro-crystals were successfully prepared. The micro-characteristics of the micro-crystals and the original drug were obviously different, and the in vitro dissolution rate was significantly accelerated. After the single-dose oral administration of Toltrazuril and microcrystal, the main drugs The kinetic parameters Cmax were (8.925 ± 0.360) mg / L and (12.510 ± 0.525) mg / L respectively, the tmax were all 24h and the AUC values were (411.605 ± 20.918) mg / (L · h) (578.650 ± 11.664) mg / (L · h), the relative bioavailability was 140.6%, and the data of the drug met the first-order absorption two-compartment model. The results showed that the HPLC method was suitable for the determination of the concentration of Tropsilzin plasma; Tropsilzin microcrystalline crystals compared with the Tropetail original drug absorption rate and absorption in vivo have greatly increased.