溴吡斯的明12h缓释片的体外释放行为相关性研究  

Correlation between in vitro release of pyridostigmine bromide slow-release tablet and its in vivo pharmacokinetics

作　　者：熊华蓉[1] 谭群友[2] 赵德璋[1] 王睿[2] 张景勍[1] 

机构地区：[1]重庆医科大学药物高校工程研究中心和生物化学与分子药理学重点实验室,重庆400016 [2]第三军医大学大坪医院野战外科研究所胸外科,重庆400042

出　　处：《第三军医大学学报》2012年第14期1411-1413,共3页Journal of Third Military Medical University

基　　金：教育部博士点基金(20095503120008);重庆市教育委员会资助项目(2009首批高等学校优秀人才资助)~~

摘　　要：目的测定溴吡斯的明缓释片的体外释放和体内药代动力学,并研究其体内外相关性。方法按《中国药典》2010版二部附录XD释放度测定第二法,以磷酸缓冲液为释放介质,采用紫外分光光度法测定溴吡斯的明的累积释放百分率。6只新西兰兔采用自身交叉给药方案,单剂量口服溴吡斯的明缓释片和普通片后,采用HPLC-紫外色谱法测定不同时间点的体内血药浓度。结果溴吡斯的明缓释片12 h体外累积释放率达98.6%,其体内药动学参数如下:tmax为(4.001±0.004)h;Cmax为(15.442±0.215)mg/L;AUC0-∞为200.557±3.357。Loo-Riegelman法计算溴吡斯的明缓释片体内外的相关性,其体内累积吸收百分率与体外累积释放百分数X建立的线性回归方程为:fa=0.485 1 fr+3.837 7,r=0.986 5,大于临界值r6,0.01(P<0.01)。结论溴吡斯的明缓释片释放行为的体内外相关性显著,通过体外释放行为可预测其体内释放动力学。Objective To study the correlation between in vitro release of pyridostigmine bromide slow-release tablet and its in vivo pharmacokinetics. Methods Accumulative release percentage of pyridostig- mine bromide slow-release tablet was assayed by ultraviolet spectroscopy with phosphate buffer as a dissolution medium according to the XD release assay in 2010 edition of Chinese Pharmacopeia. After 6 New Zealand rab- bits were given a single oral dose of pyridostigmine bromide slow-release or conventional tablet, their serum drug concentration was measured at different time points by HPLC-uhraviolet spectroscopy. Results The 12 h in vitro accumulative release rate of pyridostigmine bromide slow-release tablet was 98.6%. The main in vivo phar- macokinetic parameters for pyridostigmine bromide slow-release tablet were tmax ： 4. 001± 0. 004 h , Cmax ： 15. 442±0. 215 mg/L, and AUC0-∞ = 200. 557 ± 3. 357. The correlation between the in vitro release of pyri- dostigmine bromide slow-release tablet and its in vivo pharmacokinetics was assayed with the Loo-Riegelman method. The linear regression equation for the in vivo accumulative absorption percentage and the in vitro accu- mulative release percentage of pyridostigmine bromide slow-release tablets was fa = 0. 485 1 fr 3. 837 7, r = 0. 986 5, higher than the critical value r6 ,0. 01 （P 〈 0.01 ） . Conclusion The in vivo release of pyridostigmine bromide slow-release tablet is significantly correlated with its in vitro release. The in vitro release of pyridostig- mine bromide slow-release tablet can predict its in vivo pharmacokinetics.

关 键 词：溴吡斯的明 药代动力学 体内外相关性 

分 类 号：R944.9[医药卫生—药剂学]