西罗莫司固体分散体在Beagle犬体内的药动学研究  

Pharmacokinetics of Sirolimus Solid Dispersion Tablets in Beagle Dogs

作　　者：陈咏[1] 楼永明[2] 宋洪涛[3] 朱宏阳[1] CHEN Yong;LOU Yong-ming;SONG Hong-tao;ZHU Hong-yang(Fujian Health College,Fuzhou 350101,China;Fujian institute for Drug Control,Fuzhou 350025,China;Department of Pharmacy,Fuzhou General Hospital of Nanjing Military Command,Fuzhou 350025,China)

机构地区：[1]福建卫生职业技术学院,福建福州350101 [2]福建省药品检验所,福建福州350001 [3]南京军区福州总医院药学科,福建福州350001

出　　处：《海峡药学》2020年第1期17-19,共3页Strait Pharmaceutical Journal

基　　金：福建省自然科学基金重点课题(2013Y0074);福建卫生职业技术学院院级课题(2012-2-04);福建省教育厅中青年教师教育科研项目(JA15775)

摘　　要：目的研究自制西罗莫司固体分散片在Beagle犬体内的药动学。方法6只Beagle犬分别按单剂量给药方案和多剂量给药方案口服西罗莫司受试制剂和参比制剂;采用UPLC-MS/MS法测定Beagle犬给药后不同时间的全血血样浓度。结果西罗莫司线性范围为0.50~20.00ng·mL^-1。Beagle犬单次口服西罗莫司受试制剂和参比制剂后的C max市售片>C max自制片,T max市售片<T max自制片,相对生物利用度为(102.7±4.8)%;多次口服西罗莫司受试制剂和参比制剂后C SSmax市售片>C SSmax自制片,T max市售片<T max自制片,相对生物利用度为(98.48±3.2)%。结论6只Beagle犬分别给予相同剂量的供试制剂与参比制剂后,吸收程度生物等效,所研制的西罗莫司固体分散体峰浓度降低、谷浓度增高、血药浓度波动减小,达峰时间延长,较为明显的缓释特征。OBJECTIVE To study the pharmacokinetics of self-made sirolimus solid dispersion tablets in Beagle dogs.METHODS 6 Beagle dogs were oral ingestion respectively by single dose and multiple dose regimens for sirolimus oral test and reference preparations;the UPLC-MS/MS method used to detect the sirolimus concerntration of the whole blood samples sampling with various time from administration Beagle dogs.RESULTS A linear relationship was shown when the sirolimus concentration ranging from 0.50 to 20ng·mL^-1.The results showed that the C max market tablests was higher than the C max self-made tablests,while the T max market tablests was lower than the T max self-made tablests,and the relative bioavailability was(102.7±4.8)%under Beagle dogs single oral sirolimus test and reference preparations conditions.The results of multiple oral preparations showed that the C SSmax market tablests was higher than the C SSmax self-made tablests,while the T max market tablests was lower than the T max self-made tablests,and the relative bioavailability was(94.48±3.2)%.CONCLUSION The sirolimus absorption degree of 6 beagle dogs was shown bioequivalent under the conditions of given the same dose of test and reference preparations.The self-made SRL solid dispersion showed sustained release characteristics obviously with peak concentration decreased,trough concentration increased,blood concentration fluctuation,the peak time prolonged respectively.

关 键 词：西罗莫司 UPLC-MS/MS 固体分散体 单剂量和多剂量药动学 生物利用度 

分 类 号：R965[医药卫生—药理学]