TJ0711盐酸盐的血浆蛋白结合率及其在大鼠体内的组织分布  

The binding rates of TJ0711 hydrochloride to human and rat plasma proteins and its tissue distribution in rats

作　　者：马一鸣[1] 范昭泽[1] 陈旭[1] 胡磊[1] 翟雪珍[1] 李高[1] 斯陆勤[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《中国医院药学杂志》2011年第15期1235-1238,共4页Chinese Journal of Hospital Pharmacy

基　　金："十一五"国家重大新药创制(候选药物)(编号:2009ZX09103-146);湖北省研究与开发计划项目(编号:2008BCB103);武汉综合性新药研究开发技术大平台(编号:2009ZX09301-014)

摘　　要：目的:建立生物样品中TJ0711盐酸盐的浓度的测定方法,测定TJ0711盐酸盐在人标准血浆和大鼠血浆中的蛋白结合率,考察其在大鼠组织中的分布特性。方法:用平衡透析法测定血浆蛋白结合率,用高效液相-荧光检测法测定血浆中药物总浓度及游离药物浓度。大鼠灌胃给予TJ0711盐酸盐30 mg.kg-1,测定10,25,60,180 min TJ0711盐酸盐在各组织中的含量。结果:当TJ0711盐酸盐的血药浓度为0.5,2.0,4.0,8.0μg.mL-1时,其在大鼠血浆中的蛋白结合率分别为(88.7±2.3)%,(87.8±1.0)%,(85.8±2.0)%和(86.8±0.9)%,在人血浆中的蛋白结合率分别为(92.1±0.8)%,(89.8±1.4)%,(90.4±1.0)%和(90.4±1.7)%。药物在大鼠体内以肾、肝、肺中分布较多,脑和脂肪组织也能检测到药物,绝大多数组织的药物含量在给药后10 min或25 min最高1,80 min后药物含量显著下降。结论:TJ0711盐酸盐在人和大鼠血浆中的蛋白结合率均属于高度结合(>80%),且不随药物浓度的增加发生变化,但在人和大鼠血浆中的蛋白结合率差异具有显著性(P<0.05)。TJ0711盐酸盐在大鼠体内分布较广,可透过血脑屏障,但在各组织没有明显蓄积。OBJECTIVE To establish a HPLC method to determine the concentrations of TJ0711 in plasma and tissues for the analysis of the binding rates of TJ0711 hydrochloride to human and rat plasma proteins and its tissue distribution in rats. METHODS The binding rates of TJ0711 hydrochloride to human and rat plasma proteins were determined by equilibrium dialysis method. The concentrations of TJ0711 were assayed by HPLC with fluorescence detection. The concentrations of TJ0711 in tissue samples were determined by the same method after oral dose of 30 mg·kg^-1 in rats at time-points of 10 min, 25 min, 60 min, 180 min. RESULTS The binding rates of TJ0711 hydrochloride to rat plasma proteins at the concentrations of 0. 5, 2.0,4. 0 and 8. 0 μg·mL^-1 were （88. 7 ± 2. 3） %, （87. 8 ±1.0） %, （85.8 ±2. 0）% and （86. 8 ＋ 0. 9） %, respectively, while the binding rates of TJ0711 hydrochloride to human plasma at the above concentrations were （92. 1 ± 0. 8）%, （89. 8 ±1.4）%, （90. 4 ±1.0）% and （90. 4 ±1.7）%, respectively. After oral administration of TJ0711 hydrochloride, the higher levels were found in kidney, liver, and lung. Lower hut detectable levels were found in brain and fat tissue. The peak levels in most tissues appeared at 10 min or 25 min and drug concentrations in all tissues decreased significantly at 180 min. CONCLUSION The pro- tein binding rates of TJ0711 hydrochloride were high （〉80 %）, and independent of drug concentrations. Besides, the binding rates showed significant differences between rat and human plasma proteins （P〈0. 05）. TJ0711 hydrochloride was distributed widely in rats and could permeate the blood-brain barrier. There was no significant accumulation observed in all tissues.

关 键 词：TJ0711盐酸盐 高效液相色谱 平衡透析法 蛋白结合率 组织分布 

分 类 号：R96[医药卫生—药理学]