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、5.0 mL/kg）或多次iv给予（5.0 mL/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WinNonlin 6.3软件计算药动学参数。结果 单次iv痰热清注射液2.5 mL/kg后，黄芩苷、熊去氧胆酸和鹅去氧胆酸的t_1/2分别为（48.19±12.74）、（56.19±33.33）、（109.96±58.39）min；AUC_{0~6 h}分别为（1 718.02±656.49）、（1 150.83±371.53）、（541.52±403.69）μg?min/mL；给药量在1.25～5.0 mL/kg时，3种成分的t_1/2无剂量相关性，黄芩苷和熊去氧胆酸的AUC_{0~6 h}均与剂量呈良好的线性关系（r＞0.99），而鹅去氧胆酸的AUC_{0~6 h}与剂量呈正相关性。多次给予痰热清注射液5.0 mL/kg后，黄芩苷、熊去氧胆酸和鹅去氧胆酸的AUC_{0~6 h}分别为（2 872.37±476.45）、（3 339.63±939.94）、（1 241.29±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1.25～5.0 mL/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 t_1/2 for BC, UDCA, and CDCA were (48.19 ± 12.74), (56.19 ± 33.33), and (109.96 ± 58.39) min, and AUC_{0—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 of t_1/2 for the three major bioactive components were not affected by the dose, and AUC_{0—6 h} for BC and UDCA showed a good linearity to the dosage (r > 0.99), but AUC_{0—6 h} of CDCA was positively correlated with the dosage. After multiple iv administration of Tanreqing Injection (5.0 mL/kg), the values of AUC_{0—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.

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