Li Tao, Wang Yi-Wei, Wang Yan-Li, Zhang Dong, Zhang Hui-Hui, Chen Li, Zhuang Shuai-Xing, Zhou Zhong-Ming, Yang Wei-Peng
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beining, China.
Yao Xue Xue Bao. 2014 Oct;49(10):1418-25.
The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1β and TNF-α were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1β and TNF-α. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ≤ 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body.
在酵母诱导的发热大鼠中研究了黄芩汤（HQT）的药效学（PD）和药代动力学（PK）特性。大鼠单次口服20 g·kg⁻¹的HQT后，在不同时间点采集血液样本和直肠温度数据。采用灵敏的液相色谱 - 串联质谱（LC-MS）法对芍药苷、黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、木犀草素、甘草酸和甘草次酸的血浆浓度进行定量。通过放射免疫分析（RIA）检测PGE2、IL-1β和TNF-α的血药浓度。使用WinNonlin软件通过非房室分析处理所有药代动力学参数。通过计算Pearson相关系数研究8种成分的平均浓度与解热效果之间的潜在关系。结果发现，HQT对酵母诱导的发热大鼠具有显著的解热效果，但对正常大鼠无影响。HQT的解热作用可归因于对PGE2、IL-1β和TNF-α的抑制。发热大鼠体内的成分（黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、木犀草素、甘草酸和甘草次酸）吸收和消除延迟，在体内停留时间更长，与正常大鼠相比具有更高的C(max)和AUC。发热状态可影响HQT在体内的药代动力学行为；具有相同骨架的黄酮类化合物在体内表现出相似的命运；黄芩素和汉黄芩素与所测定的解热效果具有强正相关（R > 0.66，P ≤ 0.02）。总之，这些成分在发热机体中表现出不同的药代动力学特性。
