Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect.
Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect.
复制标题
川芎嗪乙醇体贴剂在大鼠体内的药动学及抗心肌缺血及抗缺血再灌注损伤作用
DOI：
10.2147/ijn.s20263
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发表时间：
2011
影响因子：
8
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Liu X;Liu H;Zeng Z;Zhou W;Liu J;He Z
本研究的目的是研究川芎嗪醇质体贴剂的药代动力学以及抗心肌缺血和抗缺血再灌注损伤的作用。雄性SD道利大鼠随机分为3组：A组（川芎嗪灌胃组）、B组（川芎嗪醇质体透皮贴剂组）和C组（川芎嗪常规透皮贴剂组）。处理后，在不同时间点采集血液样品和各种组织样品，如心脏、肝脏、脾脏、肺、肾脏、脑和肌肉样品。采用高效液相色谱法测定药物浓度，绘制药物浓度-时间曲线。应用药代动力学软件3 p97计算药代动力学参数和各组织中药物浓度-时间曲线下面积（AUC）。静脉注射垂体后叶素建立大鼠急性心肌缺血模型，结扎大鼠冠状动脉左前降支建立心肌缺血再灌注损伤模型，观察川芎嗪醇质体贴剂对缺血心肌及缺血再灌注损伤的影响。结果表明，川芎嗪醇质体贴剂经皮给药组AUC最高。川芎嗪醇质体贴片组全血粘度、血浆粘度、红细胞压积、红细胞聚集指数、红细胞变形指数与缺血对照组比较有显著性差异（P < 0.01）。川芎嗪醇质体贴剂可缩小长期缺血所致心肌梗死范围。川芎嗪醇质体贴剂具有缓释特性。它们可以保持稳定和持续的血药浓度，提高生物利用度，减少给药次数。该药物贴剂能降低心肌缺血大鼠的血液流变学指标，对急性缺血心肌和缺血再灌注损伤心肌有保护作用。
The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine), Group B (transdermal ligustrazine ethosome patch), and Group C (conventional transdermal ligustrazine patch). After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration–time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration–time curve (AUC) in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01). Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches have a sustained-release property. They can maintain stable and sustained blood drug concentration, increase bioavailability, and reduce administration times. The drug patch can decrease hemorheological indices of myocardial ischemia in rats, as well as protect acute ischemic myocardium and ischemia-reperfusion injured myocardium.