【作者】 高鹏；

【导师】 贾伟；

【作者基本信息】 天津大学 ， 药物分析， 2007， 硕士

【摘要】 目的:通过评价复方烟酸缓释片的动物药代动力学及生物等效性,考察其体外释放度和体内吸收度的相关性,建立该品种的质量评价体系。方法:采用高效液相色谱紫外检测法测定Beagle犬双交叉试验单剂量口服复方烟酸缓释片与烟酸普通片后血浆中烟酸的浓度,采用方差分析和双向单侧t检验进行等效性检验。对烟酸的血药浓度-时间数据用3P97药物动力学程序进行模拟,选择合适的房室模型自动计算相关参数。用释放度测定法研究复方烟酸缓释片的体外释放行为,采用相似因子法评价缓释片与普通片释放度的相似程度,并按照Wagner-Nelson方程计算各个时间点的药物体内累积吸收率,以试验品体外释放百分率对体内吸收百分率在相应的时间点进行体内外相关性的研究。结果:单次给药后主要药物动力学参数表明,缓释片和普通片中烟酸的Tmax分别为(2.58±0.92)h和(1.00±0.17)h; Cmax分别为(107.8±10.12)μg·ml-1和(205.91±28.64)μg·ml-1;AUC(0～10h)分别为(469.3±75.45)μg·h·ml-1和(507.31±47.56)μg·h·ml-1; MRT分别为(1.88±0.84)h和(1.06±0.26)h。试验品与参比品中烟酸单次给药的相对生物利用度为91.16%。两种制剂的相似因子为24.03,经3P97拟合,复方烟酸缓释片中烟酸体内过程符合一室模型,试验品体外释放百分率与体内吸收百分率相关系数为0.9922。结论:单次给药试验所获得的缓释片与普通片中烟酸的AUC(0-10h)、Cmax经双向单侧t检验,Tmax和MRT用配对t检验分析,结果显示,两种制剂AUC(0-10h)无显著性差异,证明二者吸收程度相等.复方烟酸缓释片的Tmax和MRT长于普通片,Cmax低于普通片,说明缓释片无突释现象,有一定的缓释效果。两种制剂的体外释放行为不同,复方烟酸缓释片的体内吸收分数与体外释放度具有相关性。更多还原

【Abstract】 Aim This study was to compare the bioavailability of niotinic acid sustained release tablets and niotinic acid common tablets and to investigate the correlation between in vitro release and in vivo absorption of two tablets.Methods The concentration of niotinic acid in plasma was determined by RP-HPLC method with UV-detection after single and multiple oral doses of tablets to 6 BeaGLE dog. The study was designed in a crossover, random, two-treatment, two-period test, the bioequivalence of the two formulations was evaluated by ANONA and two one-side t test. All data were treated by the Practical Pharmacokinetic Program Version 97 (3p97) and pharmacokinetic parameters were calculated. The in vitro release characteristics of two formulations were studied by determining their dissolution and evaluated with similarity factor method. The absorbed fractions were calculated by Wagner-Nelson’s formula, and a linear correlation was evaluated by using percent dissoluted data and percent absorbed data from two formulations at the corresponding times.Results The pharmacokinetic parameters obtained after single oral administration of the two niotinic acid sustained release tablets were as following: The Tmax were (2.58±0.92)h and (1.00±0.17)h, Cmax were (107.8±10.12)μg·ml-1and (205.91±28.64)μg·ml-1, AUC(0-108h) were (469.3±75.45)μg·h·ml-1 and (507.31±47.56)μg·h·ml-1,MRT were (1.88±0.84)h and (1.06±0.26)h for test and reference tablets, respectively. The relative bioavailability of the test tablet was 91.16%. The similar factor was 24.03.After calculated by 3P97 software, the pharmacokinetic process of Niotinic acid sustained release tablets accord with one-compartment model, the correlation coeffcients are 0.9922 for test tablets.Conclusion The pharmacokinetic parameters obtained after single oral administration of the compound niotinic acid sustained release tablets and nicotinic acid common tablet showed that there were no significant difference between two formulations in AUC0-10, and there there were signifigant difference in Cmax, Tmax and MRT. The sustained release tablet was bioequivalent to RT and compound niotinic acid sustained release tablets possessed good sustained release property. The dissolution rates between two formulations were different and the dissolution was similar. The results of correlation test showed the compoumd nicotinic acid sustained release tablets had a satisfactory correlation between dissolution in vitro and absorption in vivo.更多还原