赛西尼在大鼠体内药代动力学和生物利用度研究

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (3): 254-259.

赛西尼在大鼠体内药代动力学和生物利用度研究

邹全飞^1,3, 陆榕^2,3, 樊慧蓉^2,3, 赵广荣¹, 张铁军², 司端运^2,3

¹天津大学,天津 300072;
²天津药物研究院,天津 300193;
³释药技术与药代动力学国家重点实验室,天津 300193

收稿日期:2013-03-31 修回日期:2014-01-10 出版日期:2014-03-26 发布日期:2014-04-10
通讯作者: 司端运,男,博士,研究员,研究方向:药物代谢动力学。Tel: 022-84845261 E-mail: ddysi@sohu.com
作者简介:邹全飞,女,硕士研究生,研究方向:药物代谢动力学。Tel: 13820759961 E-mail: fully18@126.com
基金资助:
重大专项(2010ZX09304002; 2012ZX09501001002)和“973”项目(2010CB933902)

Study of pharmacokinetics and bioavailability of scicinib in rats

ZOU Quan-fei^1,3, LU Rong^2,3, FAN Hui-rong^2,3, ZHAO Guang-rong¹, ZHANG Tie-jun², SI Duan-yun^2,3

¹Tianjin University , Tianjin 300072,China;
²Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China;
³State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin 300193, China

Received:2013-03-31 Revised:2014-01-10 Online:2014-03-26 Published:2014-04-10

摘要/Abstract

摘要： 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,AUC_0-T与剂量呈正相关,t_1/2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AUC_0-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。

关键词: 赛西尼, LC/MS/MS, 药代动力学, 生物利用度

Abstract: 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, 40 mg/kg and intravenous injected scicinib at the dose of 5 mg/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, 20 and 40 mg/kg). The AUC_0-T was linearly increased with the increase of dosage in rats, while t_1/2 was not varied,the t_1/2 was (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 5 mg/kg was 20.4%.CONCLUSION: The pharmacokinetic behavior of scicinib showes the first-order kinetics characteristics after the dosage of 5-40 mg/kg, and the absolute bioavailability was well accepted.

Key words: scicinib, LC/MS/MS, pharmacokinetic, bioavailability

中图分类号:

R965.2

邹全飞, 陆榕, 樊慧蓉, 赵广荣, 张铁军, 司端运. 赛西尼在大鼠体内药代动力学和生物利用度研究[J]. 中国临床药理学与治疗学, 2014, 19(3): 254-259.

ZOU Quan-fei, LU Rong, FAN Hui-rong, ZHAO Guang-rong, ZHANG Tie-jun, SI Duan-yun. Study of pharmacokinetics and bioavailability of scicinib in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 254-259.

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