酒石酸美托洛尔渗透泵控释片比格犬体内药动学研究  

Pharmacokinetic Study of Metoprolol Tartrate Osmotic Pump Controlled-Release Tablets

作　　者：龚伟[1] 李阳[1] 刘燕[1] 衣伟峰[1] 梅兴国[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《解放军药学学报》2014年第1期22-25,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：国家十二五重大专项;No.2012ZX09301003-001-009

摘　　要：目的以酒石酸美托洛尔普通片作为参比制剂,研究酒石酸美托洛尔渗透泵控释片比格犬体内药动学特征。方法采用自身对照交叉试验设计,比较研究比格犬单剂量口服酒石酸美托洛尔渗透泵控释片与普通片的药动学特征,采用HPLC-MS测定比格犬血浆中酒石酸美托洛尔浓度。结果酒石酸美托洛尔渗透泵控释片和普通片的C max分别为(1124.76±318.09)和(3822.88±567.28)ng·ml-1;T max分别为(8.00±1.79)和(0.88±0.14)h;MRT分别为(11.18±2.46)和(4.54±0.84)h;AUC0-t分别为(11 773.09±3897.03)和(14 876.61±3903.03)ng·h·ml-1。酒石酸美托洛尔渗透泵控释片的体外累积释放百分数与比格犬体内药物吸收百分数之间线性相关系数为0.993。结论与普通片相比,口服酒石酸美托洛尔渗透泵控释片的C max显著降低,T max和MRT显著延长,具有明显缓释效果,体内外相关性良好。Objetive To investigate the pharmacokinetics of metoprolol tartrate osmotic pump controlled-release tablets with metoprolol tartrate tablets used as a control. Methods A comparative study of metoprolol tartrate osmotic pump controlled-release tablets and common tablets at a single oral close was conducted among six dogs according to crossover design. Metoprolol and internal standards were quantified in dog plasma using a high-performance liquid chro- matography-tandem mass spectrometry. Results The pharmacokinetic parameters of metoprolol tartrate osmotic pump con- trolled-release tablets and common tablets were as follows： C max （1124.76±318.09） and （3822.88 ±567.28） ng ·ml-1; T （8.00±1.79） and （0.88 ±0.14） h;MRT （11.18 ±2.46） and （4.54 ±0.84） h;AUC0_1（11 773.09 ±3897.03） and （ 14 876.61 ± 3903.03） ng ·h ·ml - 1. The linear correlation coefficient between the irt vitro accumulative release per- centage and in vivo absorption percentage of metoprolol tin, rate osmotic pump controlled-release tablets was 0.993 （ P 〈 0.01 ）. Conclusion The C max of the test formulation was remarkably lower than that of reference formulation. The T and MRT of the test formulation were significantly prolonged. The test formulation had more significant sustained-release effect and in vitro - in vivo correlation than the reference formulation.

关 键 词：酒石酸美托洛尔 渗透泵片 控释 药动学 

分 类 号：R969.1[医药卫生—药理学]