复方烟酸辛伐他汀双层缓释片的制备及Beagle犬体内药代动力学  

Preparation and pharmacokinetics of compound nicotinic acid extended-release and simvastatin immediate-release double-layer tablets

作　　者：周莉[1] 黎洪 尹莉芳[1] 王莎 陈西敬[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]广州白云山明兴制药有限公司,广州510250

出　　处：《中国药科大学学报》2012年第6期508-513,共6页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2009ZX09310-004);教育部新世纪优秀人才支持计划资助项目(No.NCET-08-0846);中央高校基本科研业务费专项基金资助项目(No.JKZ2009009)~~

摘　　要：以烟酸和辛伐他汀为模型药物制备复方双层缓释片,并评价其体外释放特性。采用双周期双交叉给药方案,LC-MS/MS法同时测定自制制剂和市售制剂中烟酸和辛伐他汀的血药浓度,对6只Beagle犬进行了药代动力学和生物利用度的初步研究。自制制剂和市售制剂给药后烟酸的cmax分别为(6.43±0.80)和(6.38±0.47)μg/mL,tmax分别为(2.80±1.00)和(2.50±1.00)h,AUC分别为(30.16±4.51)和(27.49±4.04)μg.h/mL;辛伐他汀的cmax分别为(38.65±1.71)和(40.54±2.33)ng/mL,tmax均为(1.50±0.40)h,AUC分别为(118.76±11.83)和(115.76±5.46)ng.h/mL。结果表明两种制剂中烟酸和辛伐他汀的AUC,cmax和tmax都等效,说明自制制剂和市售制剂在Beagle犬体内具有生物等效性。Compound nicotinic acid extended-release and simvastatin immediate-release double-layer tablets were developed and their in vitro release characteristics were evaluated.The LC-MS/MS method was established for the determination of the concentration of nicotinic acid and simvastatin in blood and investigate the pharmacokinetics and relative bioavailability in 6 Beagle dogs with the double-period and double-crossover dosage regimen.After oral administration of the test and reference tablets,cmax of nicotinic acid was（6.43±0.80） and（6.38±0.47） μg/mL;tmax was（2.80±1.00） and（2.50±1.00） h;AUC was（30.16±4.51） and（27.49±4.04） μg ·h/mL,respectively.cmax of simvastatin was（38.65±1.71） and（40.54±2.33） ng/mL;tmax was（1.50±0.40） and（1.50±0.40） h,AUC was（118.76±11.83） and（115.76±5.46） ng ·h/mL,respectively.Statistical analysis indicated that AUC,cmax and tmax of test preparations were equivalent to reference preparations.So it is bioequiavailability between the test and reference preparations in Beagle dogs.

关 键 词：烟酸 辛伐他汀 双层缓释片 药代动力学 生物利用度 

分 类 号：R944[医药卫生—药剂学] R969.1[医药卫生—药学]