药学学报, 2014, 49(10): 1418-1425
引用本文:
李涛, 王怡薇, 王彦礼, 张东, 张会会, 陈立, 庄帅星, 周钟鸣, 杨伟鹏. 黄芩汤在大鼠发热状态下药效学及药代动力学特征研究[J]. 药学学报, 2014, 49(10): 1418-1425.
LI Tao, WANG Yi-wei, WANG Yan-li, ZHANG Dong, ZHANG Hui-hui, CHEN Li, ZHUANG Shuai-xing, ZHOU Zhong-ming, YANG Wei-peng. Pharmacokinetics and pharmacodynamics of Huangqin Tang in febrile rats[J]. Acta Pharmaceutica Sinica, 2014, 49(10): 1418-1425.

黄芩汤在大鼠发热状态下药效学及药代动力学特征研究
李涛1,2, 王怡薇1, 王彦礼1, 张东1, 张会会1, 陈立1, 庄帅星1, 周钟鸣1, 杨伟鹏1
1. 中国中医科学院中药研究所, 北京 100700;
2. 中国中医科学院医学实验中心, 北京 100700
摘要:
研究发热状态下黄芩汤的药效学和药代动力学特征。大鼠酵母菌造模后,给予黄芩汤20 g·kg-1,不同时间点取血,同时测定血药浓度、炎性介质和直肠温度的变化。结果黄芩汤能降低酵母菌致发热大鼠的体温,能降低血中前列腺素PGE2、白细胞介素IL-1β和肿瘤坏死因子TNF-α的含量。发热状态下,黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、千层纸素A、甘草酸和甘草次酸等成分的吸收速率减缓,体内的清除率降低,体内滞留时间延长,Cmax和AUC增大,发热能影响黄芩汤体内的药代动力学行为;黄芩苷和汉黄芩苷,黄芩素和汉黄芩素、千层纸素A的体内过程类似,同属于中速吸收、中速消除类成分;黄芩素、汉黄芩素的血药浓度和黄芩汤解热效应之间具有较强的正相关关系。
关键词:    黄芩汤      黄酮类      LC-MS      药代动力学      药效动力学     
Pharmacokinetics and pharmacodynamics of Huangqin Tang in febrile rats
LI Tao1,2, WANG Yi-wei1, WANG Yan-li1, ZHANG Dong1, ZHANG Hui-hui1, CHEN Li1, ZHUANG Shuai-xing1, ZHOU Zhong-ming1, YANG Wei-peng1
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
2. The Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract:
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·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 Cmax 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.
Key words:    Huangqin Tang    flavonoids    LC-MS    pharmacokinetics    pharmacodynamics   
收稿日期: 2014-04-24
基金项目: 国家自然科学基金资助项目(81273662,30801542);中国中医科学院自主业务选题项目(ZZ2007046)
通讯作者: 杨伟鹏,Tel:86-10-64046469,Fax:86-10-64013996,E-mail:hrbywp@sina.com
Email: hrbywp@sina.com
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