赛西尼在大鼠体内药代动力学和生物利用度研究

Study of pharmacokinetics and bioavailability of scicinib in rats

目的：研究赛西尼在大鼠体内的药代动力学特性和绝对生物利用度。方法： 大鼠灌胃给药5、10、20、40 mg/kg和静脉注射 5 mg/kg赛西尼后，应用LC/MS/MS分析方法测定各时间的血浆原型药物浓度。采用WinNonlin软件计算药动学参数，t检验法统计实验数据，计算生物利用度。结果： 赛西尼在大鼠体内的药动学过程符合二室模型。在5、10、20、40 mg/kg剂量范围内灌胃给药后，AUC0-T与剂量呈正相关， t1/2分别为（6.26±1.26）、（5.80±4.44）、（7.16±4.40）、（7.38±3.24） h，与剂量非线性相关。比较大鼠灌胃与静脉注射 5 mg/kg赛西尼后的AUC0-T，计算赛西尼的绝对生物利用度为 20.4%。结论：赛西尼的吸收较快，吸收程度中等，在5~40 mg/kg的给药剂量下呈现一级动力学特征。

AIM：To investigate the pharmacokinetic properties of scicinib and its absolute bioavailability in vivo in rats.METHODS：With the LC/MS/MS method for the quantification of scicinib in biosamples,the concentration of scicinib in rat plasma was determined after administrated（i.g.）scicinib at the dose of 5,10,20,40mg/kg and intravenous injected scicinib at the dose of 5mg/kg.Main pharmacokinetic parameters were estimated by non-compartmental analysis using 3P97 software.Experimental data was calculated by t-test and then the absolute bioavailability was determined.RESULTS：The pharmacokinetic property of scicinib fitted two compartment model after scicinib was given to rats at a single dose（5,10,20and 40mg/kg）.The AUC0-T was linearly increased with the increase of dosage in rats,while t1/2was not varied,the t1/2was（6.26±1.26）,（5.80±4.44）,（7.16±4.40）,（7.38±3.24）h,respectively.The absolute bioavailability of scicinib after administration（i.g.）at the dose of 5mg/kg was 20.4%.CONCLUSION：The pharmacokinetic behavior of scicinib showes the first-order kinetics characteristics after the dosage of 5-40mg/ kg,and the absolute bioavailability was well accepted.