痰热清注射液的清热作用及其主要活性成分在LPS诱导发热大鼠中的药物动力学研究

目的 研究痰热清注射液的清热作用及其主要活性成分在发热大鼠体内的药物动力学变化。方法 SD大鼠随机分成4组,分别为正常对照组、发热模型对照组、正常给药组、发热模型给药组。发热模型对照组和发热模型给药组腹腔注射LPS 100μg·kg^-1造模,正常对照组和正常给药组同时给予同剂量生理盐水。所有大鼠30 min后尾静脉给5 mL·kg^-1痰热清注射液,于给药后8 h内每0.5 h测1次体温,给药后不同时间取血浆,同时从血浆中提取3种成分,LC-UV法测定黄芩苷（BG）的浓度,LC-MS法测定熊去氧胆酸（UDCA）和鹅去氧胆酸（CDCA）的浓度。采用WinNonlin 6.3计算药动学参数。结果 痰热清注射液对LPS诱导发热大鼠有显著降温作用,能使发热大鼠体温降至与正常大鼠体温接近,并且在给药后5～8 h血药浓度较低时仍有较好的降温作用。发热模型大鼠和正常大鼠iv 5 mL·kg^-1痰热清后估算BG的半衰期分别为（41.42±7.65）和（50.32±19.10）min,AUC0～τ分别为（2 411.95±523.80）和（2 187.74±447.14）μg min.mL-1,估算UDCA的半衰期分别为（60.22±14.97）和（71.85±18.82）min,AUC0～τ分别为（1 687.59±319.65）和（1 581.38±101.48）μg min·mL^-1,AUC0～∞分别为（1 754.39±311.16）和（1 659.51±110.23）μg min·mL^-1,估算CDCA的半衰期分别为（96.47±25.04）和（94.35±27.41）min,AUC0～τ分别为（407.35±87.29）和（356.89±39.16）μg min·mL^-1,结果表明发热模型大鼠和正常大鼠iv 5 mL·kg^-1痰热清后BG、UDCA和CDCA的药物动力学行为相似。结论 痰热清注射液对LPS诱导发热大鼠有显著降温作用,发热状态下大鼠静脉注射痰热清注射液不影响其主要活性成分BG、UDCA和CDCA的药物动力学行为。

Pharmacokinetics of main active ingredients of Tanreqing injection in rats with LPS induced fever and its antifebrile effects

Objective To obtain pharmacokinetic profile of baicalin （BG）, ursodeoxycholic acid （UDCA） and chenodeoxy- cholic acid （CDCA） in the plasma after intravenous administration of Tanreqing （TRQ） injection to lipopolysaccharides （LPS） induced fever in rats. The antifebrile effects of TRQ injection were also investigated. Methods Twenty-four experimental rats were randomly divided into a normal control group, a model control group, a normal group treated with TRQ and a model group treated with TRQ. Fever was induced by intraperitoneally injecting 100 μg·kg^-1 LPS. The temperature was observed every 30 rain and the observation lasted 8 h. After 30 rain of LPS injection, the model control group and the model group treated with TRQ received 5mL·kg^-1 of TRQ via caudal intravenous injection. After simultaneous extraction of the 3 major bioactive components in rat plasma, the concentration of BG was determined by LC-UV method, and UDCA as well as CDCA was determined by LC-MS method. The experimental data were analyzed with WinNonlin 6.3 software and the pharmacokinetic parameters of BG, UDCA and CDCA were evaluated. Results The pharmacokinetic parameters of BG, UDCA and CDCA did not change with fever. TRQ injection effectively decreased febrile response in LPS-induced fever in rats. Conclusion TRQ injection has antipyretic effect and fever does not change the pharmacokinetic profile ofBG, UDCA and CDCA in TRQ injection.