摘要
Objective： This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing （XNJ）. Methods： The rats were divided into two groups, ischemia-reperfusion （IR） and sham-operated （SO） rats. Each group contained two subgroups： pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion （MCAO）. The blood samples were collected punc- tually after oral administration and a specific gas chromatographic system-flame ionization detector （GC-FID） method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results： After administration of borneol, the maximum plasma concentration （Cmax） and area under the curve （AUC） values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup （P〈0.05）. Conclusions： These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.
研究目的:中风的发生对冰片药代动力学特征的影响。创新要点:首次对冰片及其中药制剂在脑取血再灌注(中风病理状态下)的药代动力学进行研究,为药物在中风治疗中的应用提供参考。研究方法:采用大脑中动脉堵塞法建立脑缺血中风模型,中风组和假手术组分别灌胃冰片与醒脑静口服制剂,不同时间点眼眶取血后用气相色谱氢火焰离子化检测器(GC-FID)测定,并用非房室模型分析药时曲线(见图3),得各药代动力学参数(见表2)。重要结论:脑取血再灌注损伤(中风状态)可以促进冰片的吸收及生物利用,醒脑静中其他成分对其药代动力学特征也有一定影响。
基金
Project supported by the Innovation Team Development Program of Beijing University of Chinese Medicine(No.2011-CXTD-13)
the Independent Project of Beijing University of Chinese Medicine(No.2013-JYBZZ-XS-093)
the Technology Major Projects of China(No.2014ZX09301306-008)
