Ginkgo diterpene lactones are compounds that are extracted from the Gi的简体中文翻译

Ginkgo diterpene lactones are compo

Ginkgo diterpene lactones are compounds that are extracted from the Ginkgo biloba leaf and possess pharmacologic activities with neuroprotective effects. To address the poor bioavailability of ginkgo diterpene lactones, ginkgo diterpene lactone meglumine injection (GDLI) was formulated and is commercially available. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the total amount and the amount of the prototype forms of ginkgolides A (GA), B (GB) and K (GK) in rat plasma and tissues. This method was used to calculate the concentrations of the hydrolysed carboxylic forms and assess the pharmacokinetics of the ginkgolides after intravenous (i.v.) GDLI administration in rats. Generally, all three ginkgolide forms showed dose-dependent plasma concentrations, and no obvious differences in pharmacokinetic parameters, i.e., area under the curve (AUC) of plasma concentration versus time and half-life, were observed after GDLI administration on 7 consecutive days. These ginkgolides primarily existed in the carboxylic form in the plasma, and the systemic concentrations of the carboxylic forms of GA and GB were 11- to 17- and 3- to 4-fold higher than those of their prototype forms, respectively. In contrast, dramatically increased levels of the GA and GB prototype lactones were detected in the liver and heart. GA, GB, and GK were extensively distributed in various organs/tissues; the highest levels were found in the kidneys, liver, and intestine, and the lowest levels were found in the brain. These data suggest that ginkgolides have difficulty crossing the blood-brain barrier and that their targets for protecting against cerebral ischaemia are located outside the central system.
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银杏二萜内酯是从银杏叶中提取的化合物,具有具有神经保护作用的药理活性。为了解决银杏二萜内酯的不良生物利用度,配制了银杏二萜内酯葡甲胺注射液(GDLI),并且可商购。在这项研究中,开发了一种简单,灵敏且可靠的液相色谱-串联质谱(LC-MS / MS)方法,并验证了该方法用于评估银杏内酯A(GA),B(GB)原型形式的总量和数量)和大鼠血浆和组织中的K(GK)。该方法用于计算大鼠中静脉内(iv)GDLI给药后水解的羧酸形式的浓度并评估银杏内酯的药代动力学。通常,这三种银杏内酯形式均显示出剂量依赖性的血浆浓度,并且连续7天服用GDLI后未观察到药代动力学参数的明显差异,即血浆浓度相对于时间和半衰期的曲线下面积(AUC)。这些银杏内酯主要以羧基形式存在于血浆中,GA和GB羧基形式的全身浓度分别比其原型形式高11至17倍和3至4倍。相反,在肝脏和心脏中检测到GA和GB原型内酯的水平急剧增加。GA,GB和GK广泛分布在各种器官/组织中。在肾脏,肝脏和肠道中发现最高水平,而在大脑中发现最低水平。
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银杏二萜内酯是从银杏叶中提取的具有药理活性和神经保护作用的化合物。为解决银杏二萜内酯生物利用度低的问题,研制了银杏二萜内酯葡胺注射液(GDLI)。本研究建立了一种简便、灵敏、可靠的液相色谱-串联质谱(LC-MS/MS)方法,并对其进行了验证,以测定银杏内酯a(GA)、B(GB)和K(GK)在大鼠血浆和组织中的总量和含量。用此方法计算大鼠静脉注射GDLI后水解羧基的浓度,并评价银杏内酯在大鼠体内的药代动力学。总的来说,三种银杏内酯剂型的血药浓度均呈剂量依赖性,连续7天给药后,药代动力学参数,即血药浓度曲线下面积(AUC)与时间和半衰期之间没有明显差异。这些银杏内酯主要以羧基形式存在于血浆中,GA和GB的羧基形式的系统浓度分别比其原型高11~17和3~4倍。肝脏组织中GA和内酯含量显著升高。GA、GB和GK广泛分布于各种器官/组织中,在肾脏、肝脏和肠道中含量最高,在大脑中最低。这些数据表明银杏内酯很难跨越血脑屏障,它们预防脑缺血的靶点位于中枢系统之外。
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