琥珀酸美托洛尔缓释片狗体内药物动力学研究  

The study of pharmacokinetics of metoprolol succinate sustained release tablets in dogs

作　　者：黄桂华[1] 张娜[1] 高彦慧[1] 邹满[2] 贺敦伟[1] 

机构地区：[1]山东大学药学院药剂学教研室,山东济南250000 [2]山东体育学院,山东济南250000

出　　处：《山东大学学报（医学版）》2004年第1期56-59,共4页Journal of Shandong University:Health Sciences

摘　　要：目的:比较琥珀酸美托洛尔缓释片和普通片狗体内相对生物利用度和体内外相关性。方法:采用单剂量自身交叉试验设计,对6条杂种狗灌胃给药,采用高效液相色谱法,荧光检测器,测定血浆中美托洛尔的浓度,通过3p97程序拟合血药浓度-时间数据,求两制剂的药动学参数,并采用方差分析、双单侧t检验和(1-2α)置信区间等分析方法评价其生物等效性;采用W-N法进行体内外相关性研究。结果:琥珀酸美托洛尔缓释片和普通片符合单室模型特征,其主要药动学参数:t1/2分别为(4.01±0.82)h和(1.74±0.14)h;Tpeak分别为(2.04±0.29)h和(0.58±0.18)h;Cmax分别为(168.1±33.1)ng/ml和(410.3±21.2)ng/ml;AUC0～∞分别为(1365.5±186.5)ng.h/ml和1472.3±190.2ng.h/ml。缓释片相对于普通片的生物利用度为97.61%,其体内吸收与体外释药具有良好的相关性(r=0.9367)。结论:琥珀酸美托洛尔缓释片与普通片两种制剂生物等效,达到了剂型设计的要求。Objective: To compare the bioavailability and correlation between in vitro release and in vivo characteristics of metoprolol succinate sustained-release tablets(MSST) and the conventional tablets(CT). Methods: MSST or CT were given orally to dogs, with a single dose of 95mg(MSST)and 100mg(CT) in a self-crossover study. The plasma concentration of metoprolol was assayed by HPLC and the pharmacokinetics parameters were calculated with 3p97 program. And the bioequivalence of parameters was valued by variance analysis, two one-side test and (1-2a)believe inter-regional analyse methods.The in vivo-in vitro correlation of metoprolol succinate sustained-release tablets in dogs was studied by W-N method. Results: Concentration-time curves of MSST and CT fitted to one-comarptment open model. t1/2 (4.01±0.82)h and (1.74±0.14)h, Tpeak (2.04±0.29)h and(0.58±0.18)h, Cmax (168.1±33.1) ng/ml and(410.3±21.2)ng/ml, AUC0～∞ (1365.5±186.5)ng.h/ml and (1472.3±190.2)ng.h/ml , respectively. The relative bioavailability of MSST was 97.61%. There was a ralationship between absorption in vivo and dissolution in vitro(r=0.9367). Conclusion: MSST has the same bioavailability as CT.

关 键 词：美托洛尔 药代动力学 色谱法 高效液相 迟效制剂 

分 类 号：R994.5[医药卫生—毒理学]