痰热清注射液中主要活性成分在大鼠体内的药动学研究  

In vivo pharmacokinetics of major bioactive components from Tanreqing Injection in rats

作　　者：胡杰利[1] 刘绍勇 张振华 易月 张基[1] 刘晓东[1] 

机构地区：[1]中国药科大学药学院药物代谢动力学重点实验室,江苏南京210009 [2]上海凯宝药业股份有限公司,上海201401

出　　处：《中草药》2013年第13期1779-1785,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重点基础研究发展计划("973"计划)(2011CB505300;2011CB505303);江苏省高等学校优秀科技创新团队资助项目

摘　　要：目的研究痰热清注射液在大鼠体内药动学特征。方法以痰热清注射液中的主要活性成分黄芩苷、熊去氧胆酸和鹅去氧胆酸的血药浓度经时过程，表征痰热清注射液在大鼠体内药动学特征。大鼠单次iv给予（1．25、2．5、5．0mL／kg）或多次iv给予（5．0mL／kg）痰热清注射液，LC-UV法测定黄芩苷的血药浓度，LC-MS法测定熊去氧胆酸和鹅去氧胆酸的血药浓度。采用WinNonlin6．3软件计算药动学参数。结果单次iv痰热清注射液2．5mL／kg后，黄芩苷、熊去氧胆酸和鹅去氧胆酸的t1／2分别为（48．19±12．74）、（56．19±33．33）、（109．96±58．39）min；AUCo-6b分别为（1718．02±656．49）、（1150．83±371．53）、（541．52±403．69）μg·min／mL；给药量在1．25～5．0mL／kg时，3种成分的t1／2无剂量相关性，黄芩苷和熊去氧胆酸的AUCo~6h均与剂量呈良好的线性关系（r〉0．99），而鹅去氧胆酸的AUCo“h与剂量呈正相关性。多次给予痰热清注射液5．0mL／kg后，黄芩苷、熊去氧胆酸和鹅去氧胆酸的AUC0～6b分别为（2872．37±476．45）、（3339．63±939．94）、（1241．29±408．38）μg·min／mL；蓄积常数分别为83．3％、118．5％、168．0％。结论单次给于痰热清注射液1．25～5．0mL／kg后，黄芩苷和熊去氧胆酸在大鼠体内的消除过程是线性的，而鹅去氧胆酸可能是线性的。多剂量iv后，黄芩苷和熊去氧胆酸的血药浓度无明显蓄积现象，而鹅去氧胆酸有一定的蓄积倾向。Objective To investigate the in vivo pharmacokinetic characteristics of Tanreqing Injection in rats. Methods Using baicalin （BC）, ursodeoxycholic acid （UDCA）, and chenodeoxycholic acid （CDCA） in Tanreqing Injection as biomarkers to characterize the in vivo pharmacokinetics. Rats were received an iv administration of Tanreqing Injection in single dose （1.25, 2.5, and 5.0 mL/kg） or multiple doses （5,0 mL/kg）, and the blood concentration of BC was determined using LC-UV method, and the concentration of UDCA and CDCA was determined using LC-MS method. The pharmacokinetic parameters were analyzed by WinNonlin 6.3 software. Results After a single iv administration of Tanreqing Injection （2.5 mL/kg） to rats, the values of tl/2 for BC, UDCA, and CDCA were （48.19± 12.74）, （56.19±33.33）, and （109.96± 58.39） min, and AUC0-6 h were （1 718.02±656.49）, （1 150.83 ± 371.53）, and （541.52± 403.69） μg·min/mL. Within the tested dose range from 1.25 to 5.0 mL/kg, the values oftl/2 for the three major bioactive components were not affected by the dose, and AUC0-6 h for BC and UDCA showed a good linearity to the dosage （r 〉 0.99）, but AUC0-6 h of CDCA was positively correlated with the dosage. After multiple iv administration of Tanreqing Injection （5.0 mL/kg）, the values of AUC0-6 h for BC, UDCA, and CDCA were （2 872.37 ± 476.45）, （3 339.63 ± 939.94）, and （1 241.29± 408.38） μg·min/mL, and the accumulation index values were 83.3%, 118.5%, and 168.0%, respectively. Conclusion The elimination of BC and UDCA after single iv administration （1.25-5.0 mL/kg） is linear, and CDCA is probably linear after the administration. There is no significant accumulation in blood concentration for BC and UDCA, but CDCA has a tendency of accumulation after the multiple injection.

关 键 词：痰热清注射液 黄芩苷 熊去氧胆酸 鹅去氧胆酸 药动学 血药浓度 

分 类 号：R969.1[医药卫生—药理学]