阿魏酸是中藥材當歸的重要指標成分，許多文獻證實阿魏酸具有減
輕運動疲勞的症狀、抗發炎、抗氧化及預防動脈粥狀硬化發生等藥理作
用。本研究探討不同運動模式對阿魏酸之藥物動力學影響。
本實驗建立一個敏感及簡單的HPLC 分析方法，進行血漿中阿魏酸
的濃度測定。分析條件為Hitachi L-2130 HPLC 搭配光電二極體偵測器及
C18 逆相層析管柱，波長設定為260 nm 及320 nm，以Methyl paraben 做
為內部標準品，移動相為冰醋酸緩衝溶液：甲醇＝65：35 (v/v)，流速為
1mL/min，檢品注射量為50 μL。血漿之檢量線濃度範圍為0.05~5
μg/mL，線性相關係數為r2＝0.9999。日內及日間精密度RSD%皆小於
5%，回收率大於85%。
利用大鼠進行不同運動訓練 (不運動、跑步及游泳) 模式ㄧ個月
後，口服給予單次劑量當歸萃取物，經分析血中阿魏酸濃度，以進行藥
物動力學研究。阿魏酸以一室模式配適結果顯示，血中濃度對時間曲線
下之面積 (AUC) 跑步組顯著高於控制組，而清除率 (Cl_F) 則跑步組明
顯低於控制組，其他的藥動參數在各組之間皆無顯著差異。

Ferulic acid is an active constituent found in the root of Angelica sinesis
Diels. Several studies have reported that ferulic acid possesses various
pharmaceutical activites, including anti-sports-fatige, anti-inflammatory,
anti-oxidation and the prevention of atherosclerosis. The present study is to
investigate the effects of different modes of exercise on pharmacokinetics of
ferulic acid.
A sensitive and simple HPLC method for determination of ferulic acid
in rat plasma was established and validated. A Hitach L-2130 HPLC pump
system equipped with a photodiode array detector was used to analyze the
ferulic acid on a C18 reversed-phase column at 260 and 320 nm. Methyl
paraben was applied as the internal standard. A mixture of 65% acetic acid
glacial buffer and 35% methanol was used as mobile phase at a flow rate of 1
mL/min and an injection volume of 50 μl. The calibration curve is linear at
the concentration ranged from 0.05 ~ 5 μg/mL. The correlation coefficient of
the linear regression analysis was higher than 0.9999. The intra day and inter
day relative standard deviations (R.S.D.%) were below 5%. The analytical
recovery is higher than 85%.
The established HPLC method was further applied for investigating
effects of different exercise modes (sedentary, running and swimming) on
pharmacokinetics of ferulic acid in rats. After training for one month, the rats
were subjected to oral administration (single dose) of extract of Angelica
sinesis Diels. The pharmacokinetic of ferulic acid was well described by a
one compartment model. Area under the curve (AUC) of running group was
significantly higher than sedentary group. Clearance (Cl_F) of running group
was significantly lower than sedentary group. In addition to AUC and CL_F,
there were no significant differences on other pharmacokinetic parameters
among three groups.

誌謝 I
中文摘要 II
Abstract III
目錄 IV
表目錄 VIII
圖目錄 X
第壹章 文獻回顧 1
第一節 緒言 1
第二節 當歸簡介 2
第三節 阿魏酸的來源植物及理化性質 3
(一) 阿魏酸的來源植物 3
(二) 阿魏酸的理化性質 3
第四節 阿魏酸的藥理活性 5
(一) 抗氧化活性 5
(二) 抗發炎及抗菌作用 5
(三) 對血液之作用 6
(四) 鎮靜催眠作用 6
(五) 降低膽固醇活性 6
(六) 神經保護作用 6
(七) 抗癌活性 7
第五節 阿魏酸的藥物動力學性質 8
(一) 阿魏酸的吸收 8
(二) 阿魏酸的分佈 8
(三) 阿魏酸的代謝 8
(四) 阿魏酸的排泄 8
第六節 阿魏酸血漿中分析方法相關研究 9
第七節 運動對藥物動力學的影響 11
(一) 運動對藥物吸收的影響 11
(二) 運動對藥物分佈的影響 11
(三) 運動對藥物代謝的影響 12
(四) 運動對藥物排泄的影響 12
第八節 研究動機 13
第貳章 血漿中阿魏酸分析方法建立與確效 14
第一節 實驗材料 14
(一) 當歸 14
(二) 實驗藥品及試劑 14
(三) 儀器及材料 15
第二節 實驗方法 16
(一) 當歸萃取 16
(二) 當歸乙醇萃取物中阿魏酸定量 16
(三) Ferulic acid血漿檢品之HPLC方法確效 17
第三節 結果與討論 20
(一) 當歸乙醇萃取物中Ferulic acid定量分析 20
(二) Ferulic acid血漿檢品之HPLC方法確效 20
第參章 不同運動模式對阿魏酸藥物動力學影響 23
第一節 實驗材料 23
(一)運動訓練設備 23
(二)藥品及耗材 23
(三)實驗動物 23
第二節 實驗方法 24
(一) 大鼠訓練計畫 24
(二) 實驗設計 24
(三) 大鼠血液檢品Ferulic acid萃取方法 25
(四) 數據處裡與統計方法 25
第三節 結果與討論 26
(一)大鼠體重 26
(二) Ferulic acid血中濃度變化 26
(三) Ferulic acid在大鼠體內之藥物動力學 26
第肆章 總結 28
(一) Ferulic acid血中HPLC分析方法建立與確效 28
(二)運動對Ferulic acid藥物動力學影響之探討 28
附錄一 各表所列藥物動力學參數說明(一室模式) 67
附錄二 各表所列藥物動力學參數說明(非分室模式) 68
附錄三 各表所列藥物動力學參數說明 69
參考文獻 70

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