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.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
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)~~
关键词
溴吡斯的明
药代动力学
体内外相关性
pyridostigmine bromide
pharmacokinetics
in vitro-in vivo correlation
