part1.Cinnamophilin 在大鼠體內的藥物動力學研究
part2.Magnolol 在大鼠體內的藥物動力學研究

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Title:	part1.Cinnamophilin 在大鼠體內的藥物動力學研究 part2.Magnolol 在大鼠體內的藥物動力學研究 part1.Pharmacokinetic study of cinnamophilin in rats. part2.Pharmacokinetic study of magnolol in rats
Authors:	楊智鈞;Chih-Chun Yang
Contributors:	藥學院藥學系碩士班
Keywords:	菲律賓樟樹;缺血性中風;藥物動力學;Cinnamophilin;ischemic stroke;pharmacokinetic
Date:	2010
Issue Date:	2010-09-29 14:16:03 (UTC+8)
Abstract:	Cinnamophilin是從菲律賓樟樹( Cinnamomum philippinense )分離而萃取出來的化合物，為一強而有效之自然抗氧化劑與自由基截取劑，且可抑制血小板聚集，對於急性缺血性腦中風後的神經行為表現有改善的作用。極有潛力發展成為治療急性缺血性中風的藥物。本研究以大鼠為動物模型，分成兩組，靜脈給予不同劑量分別為40mg/kg和80mg/kg ，給藥後 5, 15, 30, 60, 120, 240分鐘及20小時採集血液、取腦等組織，利用高效液相層析系統來定量血液及組織中CINN原型及其結合態代謝物。結果顯示靜脈注射後CINN快速被吸收及代謝，給藥後20小時，血中仍然可以偵測到代謝物的存在，我們發現在血漿中有兩種代謝物，而主要的是葡萄糖醛基結合態代謝物，比較兩種劑量的AUC結果發現， CINN在大鼠體內的吸收有劑量依賴的情形。另外，在腦中也有發現CINN原型藥物的存在，表示其確實可通過血腦障壁，但是在給藥60分鐘後就偵測不到。此研究結果提供一個以大鼠為模型的CINN 藥物動力學研究，可以初步的了解CINN的代謝及組織分佈，提供一些資訊，也許未來可以利用藥物結構的修飾來增加藥物的吸收。 Cinnamophilin (CINN) isolated from Cinnamomum philippinense, is a strong novel antioxidant and free radical scavenger .It can decrease platelet aggregation and improve the post-stroke neurobehavioral outcome. CINN has the potential to develop into a new drug for treating acute ischemic stroke. In this study, we use Sprague-Dawley rats for the pharmacokinetic model. They were divided into two groups and administrated via jugular vein injection at dose 40 and 80 mg/kg CINN respectively. Blood and tissue samples were collected at times of 5, 15, 30, 60, 120, 240mins and 20 hrs after intravenous administration. Then CINN and its metabolites in blood or tissue were detected by a high-performance liquid chromatography system. The results showed that CINN was absorbed and metabolized rapidly in blood and its metabolites had been detected at 20 hours after administration. We found two metabolites of CINN in plasma, and the CINN glucuronides is the major metabolite. Comparison of two different doses of AUC data, we found that the dose-dependent relationship exists in the absorption of CINN. In addition, we found CINN in the brain tissue. It was proved that CINN can cross the blood-brain barrier but could not be detected at 60 min after administration. The result provides an animal model for the pharmacokinetic study of CINN. It helps us to understand metabolism and distribution of CINN and is useful to modify chemical structure of CINN and increase its activity.
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