家兔体内泊那替尼固体脂质纳米粒药代动力学研究

Pharmacokinetics Study of Ponatinib Solid Lipid Nanoparticles in Rabbits

目的探讨泊那替尼固体脂质纳米粒(P-SLN)在体内的药代动力学行为。方法将12只新西兰兔随机分为制剂组和对照组,分别给予等剂量P-SLN和泊那替尼对照品溶液,采用高效液相色谱(HPLC)法检测泊那替尼体内血药浓度,并采用DAS 2. 0药代动力学软件对所得血药浓度数据进行拟合,得出对照组和给药组的药代动力学参数。结果 HPLC法适合于检测泊那替尼血药浓度,给药组药时曲线下面积(AUC)及AUMC分别是对照组的3. 39倍和14. 87倍,清除率为0. 29倍,体内平均滞留时间为4. 55倍,半衰期为4. 44倍。结论 P-SLN在体内缓释效果明显,可显著提高泊那替尼的生物利用度,可作为药物的新剂型。

Objective To evaluate the pharmacokinetic behavior of ponatinib solid lipid nanoparticles( P-SLN) in vivo. Methods A total of 12 New Zealand rabbits were randomly divided into the preparation group and the control group. The two groups were administrated equal doses of P-SLN and ponatinib control solution respectively. The blood concentration of ponatinib were detected by high performance liquid chromatography( HPLC) and DAS 2. 0 was adopted in fit the pharmacokinetic parameters. Results The HPLC method was suitable for detecting the concentration of ponatinib. Compared with the control group,the AUC and AUMC were 3. 39 and 14. 87 times in the preparation group,the clearance rate( CL) was 0. 29 times,the mean retention time( MRT) was 4. 55 times and the half-life( t1/2) was 4. 44 times,respectively. Conclusion P-SLN has a significant sustained release effect in vivo and could significantly improve the bioavailability of ponatinib,which could be applied as a new pharmaceutical of ponatinib.