盐酸拉贝洛尔缓释片在犬体内的药代动力学研究  

Pharmacokinetic Study on the Sustained-release Tablets of Labetalol in Dogs

作　　者：孙建国[1] 王广基[1] 杨海涛[1] 山莽挺[1] 蔡晓辉[1] 

机构地区：[1]中国药科大学新中新药研究开发中心,南京210038

出　　处：《中国药科大学学报》2003年第6期529-533,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.39970 86 2)~~

摘　　要：目的 :研究盐酸拉贝洛尔缓释片在犬体内单剂量和多剂量口服给药后的药代动力学过程。方法 :采用反相高效液相色谱法测定犬血浆中拉贝洛尔的浓度。流动相为乙腈 0 0 1mol/L磷酸二氢钠 (2 8∶72 ) ,色谱柱为ShimadzuVP ODS ,5μ ,150mm× 4 6mmI D ,检测波长 2 18nm ,流速 1 2ml/min。动物试验分别采用 12只健康成年犬 ,进行单剂量和多剂量给药 ,并于相应的时间点取血测定血浆中的药物浓度。结果 :所建立的HPLC UV方法的最低检测浓度为 0 10 μg/ml。 12只犬按性别和体重区组随机口服两种拉贝洛尔制剂后 (均为 10 0mg) ,测得普通片和缓释片拉贝洛尔的药动学参数分别为 :k =0 1187± 0 0 755h-1 和 0 0 984± 0 0 2 55h-1 ,tmax1 15± 0 49h和 3 83± 1 17h ,cmax3 19± 0 42和 1 97± 0 84μg/ml。另采用 12只犬按性别和体重区组随机实验设计多剂量口服两种拉贝洛尔制剂 ,5d后血药浓度达到稳态水平 ,受试制剂和参比制剂的css分别为 1 84± 0 54和1 99± 0 2 9μg/ml(经剂量校正 )。 结论 :缓释片与普通片相比 ,达峰时间有所延长 ,达峰浓度有所降低 ,多剂量给药后缓释片每天 2次和普通片每天 3次给药的波动度无差异 ,说明缓释片具有一定的缓释效果 ,多剂量给药后拉贝洛尔在犬体内的药代动力?AIM:To study the pharmacokinetics of sustained-re lease labetalol tablets in dog.METHOD:Labetalol was measured by HP LC using Shimadzu VP-O D S column (5 μm, 150 mm×4 6 mm ID ) as stationary phase and acetonitrile-0 01 mo l/L NaH 2 PO 4 (28∶72) as mobile phase In this experiment we studied the pharmacokinetics and bioavailability of labetalol in dog after a single and multiple dose of sustained-released tablets (the test formulation) or l abetalol conventional tablets (the reference formulation) respectively RESULT : The HP LC method proved to be linear in the range of 0 10～10 0 μg/ml The lower li mit of quantitation is 0 01 μg/ml(S/N>3) The pharmacokinetic parameters after s i ngle dose are k=0 1187±0 0755 h -1 and 0 0984±0 0255 h -1 ,t max =1 15±0 49 h and 3 83±1 17 h,c max =3 19±0 42 μg/ml and 1 97±0 84 μ g/ml for reference and for test formulation respectively After 5 consecutive day, treated with the two formulations, the concentration of labetalol gets to a ste ady-state level, with the c ss of 1 84±0 54 and 1 77±0 56 μ g/ml (aft er dosage adjusted) for reference and test formulation respectively CONCLUSION: The sustained-release tablets of labetalol shows a delayed t max and lower c max The conc entration fluctuation is not larger than that of the conventional formula tion The test tablet of labetalol shows an sustained-release profile compared w ith that of conventional tablet

关 键 词：盐酸拉贝洛尔 缓释片剂 药代动力学 反相高效液相色谱法 

分 类 号：R965[医药卫生—药理学]