(3.236.222.124) 您好!臺灣時間:2021/05/11 10:02
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:王莉萱
研究生(外文):Li-Hsuan Wang
論文名稱:Levodopa與CaffeicAcid之藥物交互作用
論文名稱(外文):Drug Interaction of Levodopa with Caffeic Acid
指導教授:林淑娟林淑娟引用關係
學位類別:博士
校院名稱:臺北醫學大學
系所名稱:藥學系(博士班)
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:195
中文關鍵詞:Caffeic acidLevodopa藥物交互作用藥物動力學
外文關鍵詞:Caffeic acidLevodopaDrug-interactionPharmacokinetics
相關次數:
  • 被引用被引用:2
  • 點閱點閱:623
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
本研究的目的以家兔為實驗動物,同時以肌肉注射方式給與L-dopa/carbidopa及caffeic acid,以研究它們之間是否會產生交互作用。
首先,將L-dopa以肌肉注射方式投予家兔,探討L-dopa劑量依存性之藥物動力學。先以三種不同劑量的L-dopa/carbidopa (2/0.5, 5/1.25, and 10/2.5 mg•kg-1)經肌肉注射及經靜脈注射一種劑量之L-dopa/carbidopa (2/0.5 mg•kg-1),依交叉試驗方式分別投予六隻雄性兔子,在投藥後採血,取血漿樣品並以高壓液相層析儀分析L-dopa及3-O-methyldopa (L-dopa 之代謝物, 3-OMD)之濃度,再經由所得之數據決定L-dopa與3-OMD之藥物動力學之模式。由結果得知,L-dopa經肌肉注射後會被快速吸收,並於30分鐘內達到最高濃度,但3-OMD的形成則較慢,須於120-180分鐘後才達到最高點。L-Dopa經肌肉注射後之生體可用率為0.70-1.21,而3-OMD 形成之相對比率為 0.79-1.24;另於不同劑量間,L-dopa之肌肉注射生體可用率及3-OMD形成比率並不具統計上的差異。此外,L-dopa與3-OMD於排除半衰期上也不具統計上的差異;而在曲線下面積(AUC)及血漿中最高濃度值(Cmax),L-dopa與3-OMD於L-dopa/carbidopa在2/0.5-10/2.5 mg•kg-1劑量範圍內亦呈現正比增加之現象。由此可知,L-dopa與3-OMD在此劑量範圍內無劑量依存性之藥物動力學現象。
此外,對於caffeic acid 與 L-dopa 之交互作用實驗,首先將六隻家兔以交叉投予方式(crossover),分別以肌肉注射投予單一劑量之L-dopa/carbidopa (5/1.25 mg•kg-1)或caffeic acid (5 mg•kg-1),接著再同時投予 L-dopa/carbidopa (5/1.25 mg•kg-1) 與三種不同劑量之caffeic acid (分別為 2.5, 5 及10 mg•kg-1),而後採血分析血中 L-dopa、3-OMD、caffeic acid 及 ferulic acid 之濃度,並計算其相關之藥物動力學參數,結果得到當投予10 mg•kg-1的caffeic acid時,不僅3-OMD的形成會降低22%,而且3-OMD之Cmax會下降31%;此外L-dopa之代謝率(Metabolic ratio, AUC of 3-OMD/AUC of L-dopa) 也會減少22%。此結果顯示,caffeic acid可有意義的減少3-OMD之形成(p < 0.05),但L-dopa/carbidopa則對caffeic acid 及ferulic acid的藥物動力學參數則沒有影響,因此我們認為L-dopa/carbidopa與10 mg•kg-1的caffeic acid同時投予時會明顯的影響L-dopa經COMT pathway的代謝。
由於當 L-dopa/carbidopa與caffeic acid同時投藥時 L-dopa 的血中濃度雖有增加趨勢,但因變異性太大而未達到統計學上之有意義的差異,因此將 caffeic acid 提高劑量投予,評估能否增加 caffeic acid的影響。之後,再分別投予其他多酚類化合物,包括: dihydrocaffeic acid 與 catechin,評估其是否亦有交互作用的存在。將六隻家兔以交叉投予方式(crossover),分別以肌肉注射投予單一劑量之L-dopa/carbidopa (5/1.25 mg•kg-1),而後再同時投予 L-dopa/carbidopa (5/1.25 mg•kg-1) 與高劑量(50 mg•kg-1)之三種不同化合物,caffeic acid、catechin 與dihydrocaffeic acid (DHCA),而後採血分析血中 L-dopa、3-OMD 與 carbidopa 之濃度,並計算其相關之藥物動力學參數,結果得到當 L-dopa 分別與高劑量的 caffeic acid、dihydrocaffeic acid (DHCA)與 catechin併用後,所得L-dopa 之 AUC0-t、AUC0-?V 與 Cmax 皆比單獨投予 L-dopa/carbidopa 結果高,而除了與 catechin 併用所得之 Cmax 數值外,其餘皆達到統計學上有意義的差異(p < 0.05)。而三種化合物影響 L-dopa 之程度則以 DHCA 最大,其AUC0-t、AUC0-?V 與 Cmax 分別增加 64%、64% 與 68%。每次投藥後,所得3-OMD 之平均AUC0-t、AUC0-?V 與 Cmax之數值皆較單獨投予L-dopa 之數值低,然而,此差異除了與 caffeic acid併用結果外,其餘數值皆達到統計學上有意義的差異 (p < 0.05)。此外,與 catechin 併用下降程度最大,其3-OMD 之AUC0-t、AUC0-?V 與 Cmax 分別減低 65%、64% 與 64%,而且catechin 亦降低 3-OMD平均代謝比率達 76%。
由於 catechin 對L-dopa 經 COMT 途徑代謝的影響程度最大,因此進一步探討投予較低劑量的 catechin時,此影響是否仍然存在。將六隻家兔以交叉投予方式(crossover),分別以肌肉注射投予單一劑量之L-dopa/carbidopa (5/1.25 mg•kg-1),而後再同時分別投予L-dopa/carbidopa (5/1.25 mg•kg-1) 及三種劑量的catechin (10 mg•kg-1、20 mg•kg-1與50 mg•kg-1),經由採血分析血中 L-dopa、3-OMD、carbidopa 與 catechin 之濃度,並計算其相關之藥物動力學參數,結果得到當 L-dopa 分別與三種不同劑量的 catechin 同時投予後,可發現當併用時,所得L-dopa 之 AUC0-t、AUC0-?V 與 Cmax皆比單獨投予 L-dopa/carbidopa 結果高,除了同時給予 50 mg•kg-1 之catechin時所得Cmax 數值以外,其餘皆可達到統計學上有意義的差異(p < 0.05)。而以與 20 mg•kg-1 之catechin 同時投予後,其AUC0-t、AUC0-?V 與 Cmax 分別增加 78%、83% 與 82%,且其增加的程度最大。3-OMD 之AUC0-t、AUC0-?V 與 Cmax所得數值亦皆較單獨投予L-dopa 之數值低,其數值皆達到統計上之有意義的差異。除了併用 10 mg•kg-1 之catechin時所得AUC0-?V 數值以外,其餘數值皆達到統計上之有意義的差異(p < 0.05),但仍以與50 mg•kg-1 之catechin 同時投予後,其AUC0-t、AUC0-?V 與 Cmax 的分別下降程度最大。而三種劑量下降3-OMD平均代謝比率的幅度分別為56%、68% 與 76%,其影響程度與catechin劑量有關。
綜合以上實驗結果可知,若巴金氏症病患在服用 L-dopa 時,也併服含有多酚類 (polyphenols, 包括: caffeic acid、DHCA 或 catechin) 之飲料或水果 (如: 綠茶飲料、咖啡或奇異果等),有可能由於多酚類化合物抑制 COMT 的作用,因此增加 L-dopa 之可用率及降低 3-OMD 之生成,相對也增加 L-dopa 之治療效果。
The purpose of this study was to investigate the drug interaction between caffeic acid and L-dopa. Both caffeic acid and L-dopa/carbidopa were simultaneously administered to rabbits via an intramuscular (IM) injection.
First, the dose-dependent pharmacokinetics of levodopa (L-dopa) was studied in rabbits via an intramuscular administration. Three different doses of L-dopa/carbidopa (2/0.5, 5/1.25, and 10/2.5 mg•kg-1) were administered to six male rabbits via an IM route, and one dose of L-dopa/carbidopa (2/0.5 mg•kg-1) was administered via an intravenous (IV) route with a washout period of 1-week between different doses in a crossover treatment protocol. Plasma samples were collected after each treatment and the concentrations of L-dopa and 3-O-methyldopa (an L-dopa metabolite, 3-OMD) were measured by a sensitive high-performance liquid chromatographic (HPLC) method. Subsequently, these measurements were used to determine the pharmacokinetic behavior of L-dopa and 3-OMD. The results indicated that the absorption of L-dopa was fast with the time to the peak within 30 min, but the formation of 3-OMD was slow with the time to the peak of 120-180 min after IM administration. The IM bioavailability of L-dopa was in the range of 0.70-1.21, and the relative ratios of the formation of 3-OMD at different doses of L-dopa were in the range of 0.79-1.24. No statistically significant difference could be observed for IM bioavailability of L-dopa or for the relative ratios of the formation of 3-OMD in this dose range. The elimination half-lives of L-dopa and 3-OMD also exhibited no significant differences for each dose after IM administration. In addition, both the area under the curve (AUC) and maximum plasma concentration (Cmax) values of L-dopa and 3-OMD increased proportionally over the dose range of 2/0.5–10/2.5 mg•kg-1 for L-dopa/carbidopa, suggesting that L-dopa and 3-OMD obeyed dose-independent pharmacokinetics.
The impacts of caffeic acid on the pharmacokinetics of L-dopa were studied in rabbits. A single dose of 5/1.25 mg•kg-1 L-dopa/carbidopa was administered alone or was co-administered with three different doses of caffeic acid (2.5, 5, and 10 mg•kg-1), or a single dose of 5 mg•kg-1 caffeic acid was administered alone via an IM route to six rabbits each in a crossover treatment protocol. Plasma levels of L-dopa, 3-O-methyldopa (3-OMD), caffeic acid, and ferulic acid were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that caffeic acid administered at a dose of 10 mg•kg-1 decreased about 22% of the peripheral formation of 3-OMD and about 31% of the Cmax of 3-OMD. In addition, the metabolic ratios (MR, AUC of 3-OMD/AUC of L-dopa) decreased by about 22%. Results also indicated that caffeic acid significantly decreased the proportion of 3-OMD (p < 0.05). In contrast, the parameters of neither caffeic acid nor ferulic acid were significantly affected by L-dopa/carbidopa. In conclusion, caffeic acid at a dose of 10 mg•kg-1 can significantly affect the COMT metabolic pathway of L-dopa.
When L-dopa/carbidopa and caffeic acid were simultaneously administered, plasma level of L-dopa was increased. Due to large variance, the value did not show statistically significant differences. Therefore, to evaluate the effect of caffeic acid in higher dose with L-dopa, the investigation was carried out. In addition, L-dopa/carbidopa was simultaneously administered with other polyphenols including dihydrocaffeic acid and catechin to evaluate the drug interactions between L-dopa and dihydrocaffeic acid or catechin. A single dose of 5/1.25 mg•kg-1 L-dopa/carbidopa was administered alone or L-dopa/carbidopa was co-administered with high dose (50 mg•kg-1) of three different compounds including caffeic acid, dihydrocaffeic acid (DHCA) and catechin via an IM route to six rabbits each in a crossover treatment protocol. Plasma levels of L-dopa, 3-O-methyldopa (3-OMD), and carbidopa were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that AUC0-t, AUC0-?V and Cmax values of L-dopa were more than the values of L-dopa after administered L-dopa alone. These data were all show statistically significant differences (p < 0.05) except the Cmax values of L-dopa for co-administered with catechin. DHCA affected L-dopa availability the most among these compounds. The AUC0-t, AUC0-?V and Cmax values of L-dopa were all increased 64%, 64% and 68%, respectively. After all treatments, AUC0-t, AUC0-?V and Cmax values of 3-OMD were less than the values of 3-OMD after administered L-dopa alone. These difference were all show statistically significant differences (p < 0.05) except the AUC0-t, AUC0-?V and Cmax values of 3-OMD for co-administered with caffeic acid. Catechin affected 3-OMD data the most among these compounds. The AUC0-t , AUC0-?V and Cmax values of 3-OMD were all decreased 65%, 64% and 64%, respectively. Besides, catechin reduced metabolic ratio of 3-OMD to 76%.
Because catechin affects L-dopa metabolism by COMT pathway the most among these compounds, it intrigues us to advance investigation whether still exists drug interaction between the lower dose of catechin and L-dopa. A single dose of 5/1.25 mg•kg-1 L-dopa/carbidopa was administered alone or L-dopa/carbidopa was co-administered with three different doses of catechin (10, 20, and 50 mg•kg-1) via an IM route to six rabbits each in a crossover treatment protocol. Plasma levels of L-dopa, 3-OMD, carbidopa and catechin were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that L-dopa was co-administered with three different doses, AUC0-t , AUC0-?V and Cmax values of L-dopa were more than the values of L-dopa after administered L-dopa alone. These data were show statistically significant differences (p < 0.05) except the Cmax values of L-dopa for co-administered with catechin (50 mg•kg-1). Catechin (20 mg•kg-1) affected L-dopa availability the most among these compounds. The AUC0-t , AUC0-?V and Cmax values of L-dopa were increased 78%, 83% and 82%, respectively. After all treatments, AUC0-t, AUC0-?V and Cmax values of 3-OMD were less than the values of 3-OMD after administered L-dopa alone. These differences all were show statistically significant differences (p < 0.05). 50 mg•kg-1 of catechin affected 3-OMD data the most among these doses. After co-administered with 10, 20 and 50 mg•kg-1 of catechin, the metabolic ratio mean of 3-OMD was decreased 56%, 68% and 76%, respectively. The effects were dependent on catechin doses.
From the above studies, we inferred that PD patients simultaneously received L-dopa and beverage or fruits containing polyphenols, the polyphenols would inhibit L-dopa metabolism by COMT pathway. Therefore, polyphenols would enhance L-dopa bioavailability and reduce 3-OMD formation, and then increased L-dopa response for PD treatment.
目錄
Figures…………………………………………………………………... v
Tables……………………………………………………………………. xiv
中文摘要………………………………………………………………… xxv
英文摘要……………………………………………………………….... xxix
壹. 緒論…………………………………………………………………. 1
貳. 實驗材料與方法……………………………………………………. 19
一. 試藥與材料…………………………………………………… 19
二. 儀器…………………………………………………………… 20
三. 試藥配製……………………………………………………… 21
1. Caffeic acid (CA) 溶液之配製…………………………… 21
2. Ferulic acid (FA) 溶液之配製…………………………… 21
3. Isoferulic acid (IFA) 溶液之配製………………………… 21
4. L-Dopa 溶液之配製………………………………………. 21
5. Carbidopa 溶液之配製(LC/MS/MS 分析)……………… 22
6. 3-O-Methyldopa (3-OMD) 溶液之配製.......................... 22
7. Acebutolol 溶液之配製(HPLC 同時分析CA、FA 及
IFA 時所使用之內標化合物)…………………………….. 23
8. Trifluoroacetic acid (TFA) 溶液之配製........................... 23
9. Nicotinuric acid 溶液之配製(LC/MS/MS 同時分析
L-dopa 及3-OMD 時所使用之內標化合物)…………... 23
四. 分析條件………………………………………………………. 25
1. HPLC 同時定量血漿中caffeic acid, ferulic acid 與
isoferulic acid 濃度的分析條件..………………………... 25
2. HPLC 同時定量血漿中L-dopa 與3-O-methyldopa
(3-OMD)濃度的分析條..…..……………………………… 25
3. LC/MS/MS 同時定量血漿中L-dopa、3-O-methyldopa
(3-OMD)與carbidopa 濃度的分析條件......................... 26
五. 檢品的製備方法(Sample Preparation) …………………… 34
ii
1. Caffeic acid, ferulic acid 與isoferulic acid 血漿檢品........ 34
2. L-Dopa 與3-O-methyldopa (3-OMD) 血漿檢品............. 34
六. 動物試驗…………………………..…………………………... 35
1. 試驗動物選擇……………………………………………... 35
2. 試驗所需用具的準備……………………………………... 35
3. Caffeic acid (7.5 mg/mL、15 mg/mL、30 mg/mL 與
150 mg/mL) 試驗溶液之配備…………………………… 35
4. L-Dopa/carbidopa (二者以4:1 之比例製備,6/1.5
mg/mL, 15/3.75 mg/mL 與30/7.5 mg/mL) 試驗溶液
之配備……………………………………………………… 35
5. (+)-Catechin (150 mg/mL) 試驗溶液之配備……………. 35
6. Dihydrocaffeic acid (150 mg/mL) 試驗溶液之配備……. 36
7. 靜脈注射給藥(Intravenous injection, IV)……………… 36
8. 肌肉注射給藥(Intramuscular injection, IM)…………… 36
七. 實驗數據之處理.................................................................. 37
1. 藥物動力學參數的計算…………………………………... 37
2. 統計分析…………………………..………………………. 38
參. 結果與討論…………………………..……………………………... 39
一. HPLC同時分析血液中caffeic acid、ferulic acid 與isoferulic
acid 分析方法之確效………………………………………… 39
1. 檢體製備………………………….. ……………………… 39
2. 標準曲線(calibration curve) 與線性(linearity)………. 40
3. 精密度(precision) 與準確度(accuracy)……………… 40
4. 最低可定量濃度(lower limitation of quantification,
LLOQ) …………………………………………………….. 41
5. 回收率(recovery) ……………………………………….. 41
6. 冰凍與解凍之安定性(freeze and thaw stability)……… 45
7. 檢體製備後安定性(post-preparation stability)………... 45
二. HPLC 同時分析血液中L-dopa 與3-O-methyldopa 分析方
法…………………………..………………………………...... 48
iii
1. 檢體製備………………………….. ……………………… 48
2. 標準曲線(calibration curve) 與線性(linearity)………. 49
3. 精密度(precision) 與準確度(accuracy)……………… 49
4. 最低可定量濃度(lower limitation of quantification,
LLOQ) …………………………..………………………… 50
5. 回收率(recovery) ……………………………………….. 50
三. LC/MS/MS 同時分析血液中L-dopa、3-O-methyldopa 與
carbidopa 分析方法………………………………………….. 54
1. 檢體製備………………………….. ……………………… 54
2. 標準曲線(calibration curve) 與線性(linearity)………. 55
3. 精密度(precision) 與準確度(accuracy)……………… 55
4. 最低可定量濃度(lower limitation of quantification,
LLOQ) …………………………..………………………… 56
四. L-Dopa/carbidopa 單一劑量(2/0.5 mg·kg-1) 靜脈投予家兔
與以不同劑量之L-dopa/carbidopa (2/0.5、5/1.25 及10/2.5
mg·kg-1) 以肌肉注射投予家兔之藥物動力學及生體可用率
研究……………………………………………………………. 59
1. 家兔血漿中L-dopa 濃度所得的藥物動力學參數.......... 59
2. 家兔血漿中3-OMD 濃度所得的藥物動力學參數.......... 60
五. L-Dopa/carbidopa 單一劑量(5/1.25 mg·kg-1)、caffeic acid
單一劑量(5 mg·kg-1) 及L-dopa/carbidopa (5/1.25
mg·kg-1) 與不同劑量caffeic acid (2.5、5 與10 mg·kg-1)
同時肌肉注射家兔之藥物動力學及藥物交互作用之影響…. 74
1. 家兔血漿中L-dopa 濃度所得的藥物動力學參數.......... 74
2. 家兔血漿中3-OMD 濃度所得的藥物動力學參數.......... 75
3. 家兔血漿中caffeic acid 與ferulic acid 濃度所得的藥
物動力學參數.............................................................. 76
4. 家兔血漿中3-OMD/L-dopa 與ferulic acid/caffeic acid
之代謝比率(metabolic ratio) 的探討………………….. 77
六. Caffeic acid 單一劑量(10 mg·kg-1) 肌肉注射投予家兔
iv
後,caffeic acid 之藥物動力學及其代謝之研究.................... 105
1. 家兔血漿中caffeic acid、ferulic acid 與isoferulic acid
濃度所得的藥物動力學參數……………………………… 107
2. 家兔血漿中ferulic acid 與isoferulic acid 的代謝比率
(metabolic ratio) 的探討…………………………………. 107
七. L-Dopa/carbidopa (5/1.25 mg·kg-1)分別與高劑量(50
mg·kg-1) 的caffeic acid、dihydrocaffeic acid (DHCA) 或
catechin 同時肌肉注射家兔之藥物動力學及藥物交互作用
之影響…………………………..…………………………….. 115
1. 家兔血漿中L-dopa濃度所得的藥物動力學參數............ 115
2. 家兔血漿中3-OMD 濃度所得的藥物動力學參數........... 116
3. 家兔血漿中carbidopa 濃度所得的藥物動力學參數........ 117
4. 家兔血漿中3-OMD/L-dopa 之代謝比率(metabolic
ratio) 的探討…………………………..………………….. 118
八. L-Dopa/carbidopa (5/1.25 mg·kg-1) 與不同劑量catechin
(10, 20 與50 mg·kg-1) 同時肌肉注射家兔之藥物動力學及
藥物交互作用之影響…………………………………………. 140
1. 家兔血漿中L-dopa 濃度所得的藥物動力學參數........... 140
2. 家兔血漿中3-OMD 濃度所得的藥物動力學參數........... 141
3. 家兔血漿中carbidopa 濃度所得的藥物動力學參數........ 142
4. 家兔血漿中catechin 濃度所得的藥物動力學參數........... 143
5. 家兔血漿中3-OMD/L-dopa 之代謝比率(metabolic
ratio) 的探討................................................................. 144
肆. 結論........................................................................................... 174
伍. 參考文獻....................................................................................
陸. 發表論文....................................................................................
178
195
1.Olanow CW, Watts RL and Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): Treatment guideline. Neurology 2001; 56 (suppl 5): s3-s88.
2.Guttman M, Kish SJ and Furukawa Y. Current concepts in the diagnosis and management of Parkinson’s disease. CMAJ 2003; 168: 293-301.
3.Menza M and Marsh L. Psychiatric issues in Parkinson’s disease. In chapter 1: Mark, MH (eds) Pathogenesis, diagnosis, and treatment, 1st edn. The Taylor & Francis Group, 2 Park Square, Milton Park, Abingdon, UK 2006, p1-17.
4.White M. ??-Synuclein misfolding and aggregation in Parkinson’s disease. Eukaryon 2007; 3: 81-86.
5.Shimura H, Hattori N, Kubo S-I, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K and Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature Genetics 2000; 25: 302-305.
6.MDVU resource library. http://www.mdvu,org/library/disease/pd/par_gen.html, retrieved on 25 January 2008.
7.Wikipedia, the free encyclopedia. http://en.wikipedia.org/wiki/Parkinson%27s_disease, retrieved on 25 January 2008.
8.Brooks DJ. The early diagnosis of Parkinson’s disease. Ann Neurol 1998; 44 (Suppl 1): s10-s18.
9.Piccini P, Morrish PK, Turjanski N, Sawle GV, Burn DJ, Weeks RA, Mark MH, Maraganore DM, Lees AJ and Brooks DJ. Dopaminergic function in familial Parkinson’s disease: a clinical and 18F-dopa positron emission tomography study. Ann Neurol 1997; 41: 222-229.
10.Seibyl JP, Marek K, Sheff K, Zoghbi S, Baldwin RM, Charney DS, vanDyck CH and Innis RB. Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson’s patients. J Nucl Med 1998; 39: 1500-1508.
11.Poewe W. The natural history of Parkinson’s disease. J Neurol 2006; 253 (Suppl 7): VII/2-VII/6.
12.Horn S and Stern MB. The comparative effects of medical therapies for Parkinson’s disease. Neurology 2004; 63 (Suppl 2): s7-s12.
13.Olanow CW. Rationale for considering that propargylamines might be neuroprotective in Parkinson’s disease. Neurology 2006; 66 (Suppl 4): s69-s79.
14.Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T and Weiner WJ. Practice parameter: neuroprotective strategies and alternative therapies for Parkinson’s disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66: 976-982.
15.Gerlach M, Youdim MBH and Riederer P. Pharmacology of selegiline. Neurology 1996; 47 (Suppl 3): s137-s145.
16.The Parkinson Study Group. Effects of tocopherol and Deprenyl on the progression of disability in early Parkinson’s disease. NEJM 1993; 328: 176-183.
17.Fernandez H H and Chen JJ. Monoamine oxidase inhibitors: current and emerging agents for Parkinson disease. Clin Neuropharmcol 2007; 30: 150-168.
18.Hung AY and Schwarzschild MA. Clinical trials for neuroprotection in Parkinson’s disease: overcoming angst and futility? Current Opinion in Neurology 2007; 20: 477-483.
19.Foley P. Gerlach M, Double KL and Riederer P. Dopamine receptor agonists in the therapy. J Neural Transm 2004; 111: 1375-1446.
20.Nyholm D. Pharmacokinetic optimization in the treatment of Parkinson’ disease. Clin Pharmacokinet 2006; 45: 109-136.
21.Jenner P. Pharmacology of dopamine agonists in the treatment of Parkinson’s disease. Neurology 2002; 58 (Suppl 1): s1-s8.
22.Clarke CE and Guttman M. Dopamine agonist monotherapy in Parkinson’s disease. The Lancet 2002; 360: 1767-1769.
23.Deleu D, Northway MG and Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet 2002; 41: 261-309.
24.Juncos JL. Levodopa: pharmacology, pharmacokinetics, and pharmacodynamics. Neurologic Clinics 1992; 10: 487-509.
25.Prada MDa, Kettler R, Zurcher and Haefely WE. Inhibition of decarboxylase and levels of dopa and 3-O-methyldopa: a comparative study of benserazide versus carbidopa in rodents and of Madopar standard versus Madopar HBS in volunteers. Eur Neurol 1987; 27 Suppl. 1: 9-20.
26.Kaakkola S, Mannisto PT, Nissinen E, Vuorela A and Mantyla R. The effect of an increased ratio of carbidopa to levodopa on the pharmacokinetics of levodopa. Acta Neurol Scand 1985; 72: 385-391.
27.Poewe WH and Wenning GK. The natural history of Parkinson’s disease. Ann Neurol 1998; 44 (Suppl 1): s1-s9.
28.Obeso JA, Rodriguez-Oroz MC, Chana P, Lera G, Rodriguez M and Olanow CW. The evolution and origin of motor complications in Parkinson’s disease. Neurology 2000; 55 (Suppl 4): s13-s20.
29.Fabbrini G, Brotchie JM, Grandas F, Nomoto M and Goetz CG. Levodopa-induced dyskinesias. Movement Disorders 2007; 22: 1379-1389.
30.Cenci MA. Dopamine dysregulation of movement control in L-DOPA-induced dyskinesia. Trends in Neurosciences 2007; 30: 236-243.
31.Laar Teus van. Levodopa-induced response fluctuations in patients with Parkinson’s disease. Strategies for management. CNS Drugs 2003; 17: 475-489.
32.Bravi D, Mouradian MM, Roberts JW, Davis TL, Sohn YH and Chase TN. Wearing-off fluctuation in Parkinson’s disease: contribution of postsynaptic mechanisms. Ann Neurol 1994; 36: 27-31.
33.Rascol O. The pharmacological therapeutic management of levodopa-induced dyskinesia in patients with Parkinson’s disease. J Neurol 2000; 247 (Suppl. 2): II/51-II/57.
34.Poewe WH, Lees AJ and Stern GM. Treatment of motor fluctuations in Parkinson’s disease with an oral sustained-release preparation of L-dopa: clinical and pharmacokinetic observations. Clin Neuropharmacol 1986; 9: 430-439.
35.Coleman RJ. Current drug therapy for Parkinson’s disease. Drugs Aging 1992; 2: 112-124.
36.Koller WC and Pahwa R. Treating motor fluctuations with controlled release levodopa preparations. Neurology 1994; 44 (Suppl. 6): s23-s28.
37.Rajput AH, Martin W, Saint-Hilaire M-H, Dorfkinger E and Pedder S. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology 1997; 49: 1066-1071.
38.Rinne UK, Larsen JP, Siden A, Worm-Petersen J and Nomecomt study group. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998; 51: 1309-1314.
39.Poewe W. The role of COMT inhibition in the treatment of Parkinson’s disease. Neurology 2004; 62 (Suppl. 1): s31-s38.
40.Waters C. Other pharmacological treatments for motor complications and dyskinesias. Movement Disorders 2005; 20 (Suppl. 11): s38-s44.
41.Youdim MBH and Riederer PF. A review of the mechanisms and role of monoamine oxidase inhibitors in Parkinson’s disease. Neurology 2004; 63 (Suppl. 2): s32-s35.
42.Ferreira JJ and Rascol O. Prevention and therapeutic strategies for levodopa-induced dyskinesias in Parkinson’s disease. Current Opinion in Neurology 2000; 13: 431-436.
43.Metman LV, Dotto PD, Munckhof van den, Fang J, Mouradian MM and Chase TN. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 1998; 50: 1323-1326.
44.Olanow CW and Stocchi F. COMT inhibitors in Parkinson’s disease. Can they prevent and/or reverse levodopa-induced motor complications? Neurology 2004; 62 (Suppl 1): s72-s81.
45.Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G,Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J and Weiner WJ. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2006; 66: 983-995.
46.Waters C. Practical issues with COMT inhibitors in Parkinson’s disease. Neurology 2000; 55 (Suppl 4): s57-s64.
47.Kieburtz K and Hubble J. Benefits of COMT inhibitors in levodopa-treated parkinsonian patients. Results of clinical trials. Neurology 2000; 55 (Suppl 4): s42-s45.
48.Goetz CG. Influence of COMT inhibition on levodopa pharmacology and therapy. Neurology 1998; 50 (Suppl 5): s26-s30.
49.Reches A and Fahn S. 3-O-methyldopa blocks dopa metabolism in rat corpus striatum. Ann Neurol 1982; 12: 267-271.
50.Gervas JJ, Muradás V, Bazán E, Aguado EG, de Yĕbenes JG. Effects of 3-OM-dopa on monoamine metabolism in rat brain. Neurology 1983; 33: 278-282.
51.Wade LA and Katzman R. 3-O-methyldopa uptake and inhibition of L-dopa at the blood-brain barrier. Life Sci 1976; 17: 131-136.
52.Reches A, Mielke LR and Fahn S. 3-O-methyldopa inhibits rotations induced by levodopa in rats after unilateral destruction of the nigrostriatal pathway. Neurology 1982; 33: 887-888.
53.Feuerstein C, Tanche M, Serre F, Gavend M, Pellat J and Perret J. Dose O-methyldopa play a role in levodopa-induced dyskinesia? Acta Neurol Scand 1977; 56: 79-82.
54.Rivera-Calimlim L, Tandon D, Anderson F and Joynt R. The clinical picture and plasma levodopa metabolite profile of parkinsonian nonresponders. Treatment with levodopa and decarboxylase inhibitors. Arch Neurol 1977; 34: 228-232.
55.Tohgi H, Abe T, Kikuchi T, Takahashi S and Nozaki Y. The significance of 3-O-methyldopa concentrations in the cerebrospinal fluid in the pathogenesis of wearing-off phenomenon in Parkinson’s disease. Neurosci Lett 1991; 132: 19-225.
56..Contin M, Martinelli P, Mochi M, Riva R, Albani F and Baruzzi A. Genetic polymorphism of catechol-O-methyltransferase and levodopa pharmacokinetic-pharmacodynamic pattern in patients with Parkinson’s disease. Movement Disord 2005; 20: 734-751.
57.Männistö PT, Tuomainen P and Tuominen RK. Different in vivo properties of three new inhibitors of catechol-O-methyltransferase in the rat. Br J Pharmacol 1992; 105: 569-574.
58.Zurcher G, Keller HH, Kettler R, et al. Ro 40-7592, a novel, very potent, and orally active inhibitor of catechol-O-methyltransferase: a pharmacological study in rats. Adv Neurol 1990; 53: 497-503.
59.Assal F, Spahr L, Hadengue A, Rubbici-Brandt L and Burkhard PR. Tolcapone and fulminant hepatitis. The Lancet 1998; 352: 958-959.
60.Brooks DJ. Safety and tolerability of COMT inhibitors. Neurology 2004; 62 (Suppl 1): s39-s46
61.Olanow CW and Watkins PB. Tolcapone: an efficacy and safety review (2007). Clinical Neuropharmacol 2007; 30: 287-294.
62.Tan EK, Tan C, Fook-Chong SMC, Lum SY, Chai A, Chung H, Shen H, Zhao Y, Teoh ML, Yih Y, Pavanni R, Chandran VR and Wong MC. Dose-dependent protective effect of coffee, tea, and smoking in Parkinson’s disease: a study in ethnic Chinese. J Neurol Sci 2003; 216: 163−167.
63.Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE and Willett WC. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 2001; 50: 56−63.
64.Pan T, Jankovic J and Le W. Potential therapeutic properties of green tea polyphenols in Parkinson’s disease. Drugs Aging 2003; 20: 711−721.
65.Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative disease: a review of their intracellular targets. Eur J Pharmacol 2006; 545: 51-64.
66.Zaveri NT. Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Life Sci 2006; 78: 2073-2080.
67.Weinreb O, Mandel S, Amit T, Youdim MBH. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s disease. J Nutr Biochem 2004; 15: 506-516.
68.Moridani MY, Scobie H, Jamshidzadeh A, Salehi P and O’brien PJ. Caffeic acid, chlorogenic acid, and dihydrocaffeic acid metabolism: glutathione conjugation formation. Drug Metab Dispos 2001; 29: 1432-1439.
69.Gonthier M-P, Verny M-A, Besson C, Rēmēsy C and Scalbert A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr 2003; 133: 1853-1859.
70.Moridani MY, Scobie H and O’brien PJ. Metabolism of caffeic acid by isolated rat hepatocytes and subcellular fractions. Toxicol Lett 2002; 133: 141-151.
71.Chen D, Wang CY, Lambert JD, Ai N, Welsh WJ and Yang CS. Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies. Biochem Pharmacol 2005; 69: 1523-1531.
72.Pietta PG, Simonetti P, Gardana C, Brusamolino A, Morazzoni P and Bombardelli E. Catechin metabolites after intake of green tea infusions. BioFactors 1998; 8: 111-118.
73.Mattila P, Hellström and Törrönen R. Phenolic acid in berries, fruits and beverages. J Agric Food Chem 2006; 54: 7193-7199.
74.Islam MS, Yoshimoto M, Yahara S, Okuno S, Ishiguro K and Yamakawa O. Idenification and characterization of foliar polyphenolic composition in sweetpotato (Ipomoea batatas L.) genotypes. J Agric Food Chem 2002; 50: 3718-3722.
75.Shahrzad S and Bitsch I. Determination of some pharmacologically active phenolic acids in juices by high-performance liquid chromatography. J Chromatogr A 1996; 741: 223-231.
76.Variyar PS, Ahmad R, Bhat R, Niyas Z and Sharma A. Flavoring components of raw monsooned Arabica coffee and their changes during radiation processing. J Agric Food Chem 2003; 51: 7945-7950.
77.Tsou MF, Hung CF, Lu HF, Wu LT, Chang SH, Chang HL, Chen GW and Chung JG. Effects of caffeic acid, chlorogenic acid and ferulic acid on growth and arylamine N-acetyltransferase activity in Shigella sonnei (group D). Microbios 2000; 101: 37-46.
78.Lo HH and Chung JG. The effects of plant phenolic, caffeic acid, chlorogenic acid and ferulic acid on arylamine N-acetyltransferase activities in human gastrointestinal microflora. Anticancer Res1999; 19: 133-139.
79.Zhou L, Li D, Wang J, Liu Y, Wu J. Antibacterial phenolic compounds from the spines of gleditsia sinensis Lam. Nat Prod Res 2007; 21: 283-291.
80.Lee HC, Jenner AM, Low CS and Lee YK. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res Microbiol 2006; 157: 876-884.
81.Harrison HF, Peterson JK, Snook ME, Bohac JR and Jackson DM.. Quantity and potential biological activity of caffeic acid in sweet potato ?氙pomoea batatas (L.)?? storage root periderm. J Agric Food Chem 2003; 51: 2943-2948.
82.Giovannini L, Migliori M, Filippi C, Origlia N, Panichi V, Falchi M, Bertelli A A and Bertelli A. Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells. Int J Tissue React 2002; 24: 53-56.
83.Thiel KD, Helbig B, Sprossig M, Klocking R and Wutzler P. Antiviral activity of enzymatically oxidized caffeic acid against herpesvirus hominis type 1 and type 2. Acta Virologica 1983; 27: 200-208.
84.Bailly F and Cotelle P. Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet. Curr Med Chem 2005; 12: 1811-1818.
85.Perez-Alvarez V, Bobadilla RA and Muriel P. Structure-hepatoprotective activity relationship of 3,4-dihydroxycinnamic acid (caffeic acid) derivatives. J Appl Toxicol 2001; 21: 527-531.
86.Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG and Kim CH. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J 2004; 18: 1670-1681.
87.Kurata R, Adachi M, Yamakawa O and Yoshimoto M. Growth suppression of human cancer cells by polyphenolic from sweetpotato (Ipomoea batatas L.) Leaves. J Agric Food Chem 2007; 55: 185-190.
88.Kono Y, Kobayashi K, Tagawa S, Adachi K, Ueda A, Sawa Y and Shibata H. Antioxidant activity of polyphenolic in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen. Biochim Biophys Acta 1997; 1335: 335-342.
89.Xu JW, Ikeda K, Kobayakawa A, Ikami T, Kayano Y, Mitani T and Yamori Y. Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells. Life Sci 2005; 76: 2861-2872.
90.Raneva V, Shimasaki H, Ishida Y, Ueta U and Niki E. Antioxidative activity of 3,4-dihydroxyphenylacetic acid and caffeic acid in rat plasma. Lipids 2001; 36: 1111-1116.
91.Nardini M, D’Aquino M, Tomassi G, Gentili V, Di Felice M and Scaccini C. Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives. Free Rad Bio Med 1995; 19: 541-552.
92.Yamada J and Tomita Y. Antimutagenic activity of caffeic acid and related compounds. Biosci Biotech Biochem 1996; 60: 328-329.
93.Lee WJ and Zhu BT. Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Carcinogenesis 2006; 27: 267-277.
94.Cheng JT, Liu IM, Tzeng TF, Chen WC, Hayakawa S and Yamamoto T. Release of beta-endorphin by caffeic acid to lower plasma glucose in streptozotocin-induced diabetic rats. Horm. Metab. Res 2003; 35: 251-258.
95.Jung UJ, Lee M-K, Park YB, Jeon S-M and Choi M-S. Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J Pharmacol Exp Ther 2006; 318: 476-483.
96.Vauzour D, Vafeiadou K, Corona G, Pollard SE, Tzounis X and Spencer JP. Champagne wine polyphenols protect primary cortical neurons against peroxynitrite-induced injury. J Agric Food Chem 2007; 55: 2854-2860.
97.Budavari S. The Merck Index: an encyclopedia of chemicals, drugs, and biologicals, 11th ed. 1989. Merck & Co., Inc. press, New Jersey; p 248,.
98.John M, Gumbinger HG and Winterhoff H. Oxidation products of caffeic acid as model substances for the antigonadotropic activity of plant extracts. Planta Med 1990; 56: 14-18.
99.Khanbabaee K and van Ree T. Tannins: classification and definition. Nat Prod Rep 2001; 18: 641-649.
100.Barnes J, Anderson LA and Phillipson JD. Herbal Medicine third edition 2007, The Pharmaceutical Press. p 621, Table 20.
101.Auger C, Al-Awwadi N, Bornet A, Rouanet J-M, Gasc F, Cros G and Teissedre P-L. Catechins and procyanidins in Mediterranean diets. Food Res Int 2004; 37: 233-245.
102.De Pascual-Teresa S, Santos-Buelga C and Rivas-Gonzalo JC. Quantitative analysis of flavan-3-ol in Spanish foodstuffs and beverages. J Agric Food Chem 2000; 48: 5331-5337.
103.Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL, Hansen RJ and Waterhouse AL. Catechin is present as metabolites in humen plasma after consumption of red wine. J Nutr 1999; 129: 1662-1668.
104.Rice-Evans CA, Miller N and Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acid. Free Radical Bio Med 1996; 20: 933-956.
105.Vinson JA, Jang J, Yang J, Dabbagh Y, Liang X, Serry M, Proch J and Cai S. Vitamins and specially flavonoids in common beverages are powerful in vitro antioxidants which enrich lower density lipoproteins and increase their oxidative resistance after ex vivo spiking in human plasma. J Agric Food Chem 1999; 37: 233-245.
106.Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP and Rice-Evans C. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys 1995; 322: 339-346.
107.Yamakoshi J, Saito M, Kataoka S and Tokutake S. Procyanidin-rich extract from grape seeds prevents cataract formation in hereditary cataractous (ICR/f) rats. J Agric Food Chem 2002; 50: 4983-4988.
108.Hara-Kudo Y, Yamasaki A, Sasaki M, Okubo T, Minai Y, Haga M, Kondo K and Sugita-Konishi Y. Antibacterial action on pathogenic bacterial spore by green tea catechins. J Sci Food Agric 2005; 85: 2354-2361.
109.Demrow HS, Slane PR and Folts JD. Coronary artery disease/platelets: administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 1995; 91: 1182-1188.
110.Xu R, Yokoyama WH, Irving D, Rein D, Walzem RL and German JB. Effects of dietary catechin and vitamin E on aortic fatty streak accumulation in hypercholesterolemic hamsters. Atherosclerosis 1998; 137: 29-36.
111.Rice-Evans. Flavonoid antioxidants. Curr Med Chem 2001; 8: 797-807.
112.Mandel S and Youdim MBH. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radical Bio Med 2004; 37: 304-317.
113.Heikkinen H, Varhe A, Laine T, Puttonen J, Kela M, Kaakkola S and Reinikainen K. Entacapone improve the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Br J Clin Pharmacol 2002; 54: 363-371.
114.Wang L-H, Hsu K-Y, Hsu F-L and Lin S-J. Simultaneous determination of caffeic acid, ferulic acid and isoferulic acid in rabbit plasma by high performance liquid chromatography. J Food Drug Anal 2008; 16: 34-40.
115.Wang L-H, Hsu K-Y, Hsu F-L and Lin S-J. A dose-dependent pharmacokinetic study of levodopa by intramuscular administration in rabbits. J Food Drug Anal, 2008; accepted.
116.Uang Y-S., Kang F-L. and Hsu K-Y. Determination of caffeic acid in rabbit plasma by high-performance liquid chromatography. J Chromatogr B 1995; 673: 43-49.
117.Wittemer SM and Veit M. Validated method for the determination of six metabolites derived from artichoke leaf extract in human plasma by high-performance liquid chromatography-coulometric-array detection. J Chromatogr B 2003; 793: 367-375.
118.FDA guidance for industry-bioanalytical methods validation, 2001, http://www.fda.gov/cder/guidance/4252fnl.htm
119.Saxer C, Niina M, Nakashima A, Nagae Y and Masuda N. Simultaneous determination of levodopa and 3-O-methyldopa in human plasma by liquid chromatography with electrochemical detection. J Chromatogr B 2004; 802: 299-305.
120.Karimi M, Carl JL, Loftin S and Perlmutter JS. Modified high-performance liquid chromatography with electrochemical detection method for plasma measurement of levodopa, 3-O-methyldopa, dopamine, carbidopa and 3,4-dihydroxyphenyl acetic acid. J Chromatogr B 2006; 836: 120-123.
121.. Rondelli I, Acerbi D, Mariotti F and Ventura P. Simultaneous determination of levodopa methyl ester, levodopa, 3-O-methyldopa and dopamine in plasma by high-performance liquid chromatography with electrochemical detection. J. Chromatogr B 1994; 653: 17-23.
122.Zürcher G, Prada MD and Dingemanse J. Assessment of catechol-O-methyltransferase activity and its inhibition in erythrocytes of animals and humans. Biomed. Chromatogr 1996; 10: 32−36.
123.Blandini F, Nappi G, Fancellu R, Mangiagalli A, Samuele A, Riboldazzi G, Calandrella D, Pacchetti C, Bono G and Martignoni E. Modifications of plasma and platelet levels of L-DOPA and its direct metabolites during treatment with tolcapone or entacapone in patients with parkinson’s disease. J. Neural Transm. 2003; 110: 911-922.
124.Keränen T, Gordin A, Harjola V-P, Karlsson M, Korpela K, Pentikäinen PJ, Rita H, Seppälä L and Wikberg T. The effect of catechol-O-methyltransferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Clin. Neuropharmacol. 1993; 16: 145-156.
125.Rojo A, Fontán A, Mena MA, Herranz A, Casado S and de Yĕbenes. Tolcapone increases plasma catecholamine levels in patients with parkinson’s disease. Parkinsonism and Related Disorders 2001; 7: 93-96.
126.Cedarbaum JM, Leger G and Guttman M. Reduction of circulating 3-O-methyldopa by inhibition of catechol-O-methyltransferase with OR-611 and OR-462 in Cynomolgus monkeys: implications for the treatment of Parkinson’s disease. Clin. Neuropharmacol. 1991; 14: 330-342.
127.Bonifati V and Meco G. New, selective catechol-O-methyltransferase inhibitors as therapeutic agents in Parkinson’s disease. Pharmacol. Ther. 1999; 81: 1-36.
128.Muller T, Woitalla D, Schulz D, Peters S, Kuhn W and Przuntek H. Tolcapone increases maximum concentration of levodopa. J. Neural. Transm. 2000; 107: 113-119.
129. Ahtila S, Kaakkola S, Gordin A, Korpela K, Heinävaara S, Karlsson M, Wikberg T, Tuomainen P and Männistö PT. Effects of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers. Clin. Neuropharmacol. 1995; 18: 46-57.
130.Heikkinen H, Varhe A, Laine T, Puttonen J, Kela M, Kaakkola S and Reinikainen K. Entacapone improve the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Br. J. Clin. Pharmacol. 2002; 54: 363-371.
131.汪佑襄 Caffeic acid 在家兔體內的藥物動態學及代謝的研究 Pharmacokinetic and metabolic study of caffeic acid in rabbits. 台北醫學院藥學研究所博士論文, 1999: p162.
132.Daly JW, Axelrod J and Witkop B. Dynamic aspects of enzymatic O-methylation and demethylation of catechols in vitro and in vivo. J Biol Chem 1960; 235: 1155-1159.
133.Creveling CR, Dalgard N, Shimizu H and Daly JW. Catechol O-methyltransferase III. m- and p-O-methylation of catecholamines and their metabolites. Mol Pharmacol 1970; 6: 691-696.
134.Creveling CR, Morris, Shimizu H, Ong HH and Daly JW. Catechol O-methyltransferase III. m- and p-O-methylation of substituted catechols. Mol Pharmacol 1972; 8: 398-409.
135.Lautala P, Ulmanen I and Taskinen J. Molecular mechanism controlling the rate and specificity of catechol O-methylation by human soluble catechol O-mehyltransferase. Mol Pharmacol 2001; 59: 393-402.
136.Bai H-W, Shim J-Y, Yu J and Zhu BT. Biochemical and molecular modeling studies of the O-methylation of various endogenous and exogenous catechol substrates catalyzed by recombinant human soluble and membrane-bound catechol-O-methyltransferase. Chem Res Toxicol 2007; 20: 1409-1425.
137.Nagai M, Conney AH and Zhu BT. Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catech-O-methyltransferase. Drug Metabo Dispos 2004; 32: 497-504.
138.Chen D, Wang CY, Lambert JD, Ai N, Welsh W and Yang CS. Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies. Biochem Pharmacol 2005; 69: 1523-1531.
139.Kadowaki M, Ootani E, Sugihara N and Furuno K. Inhibitory effects of catechin gallates on O-methyltranslation of protocatechuic acid in rat liver cytosolic preparations and cultured hepatocytes. Biol Pharm Bull 2005; 28: 1509-1513.
140.van Duursen MBM, Sanderson JT, de Jong PC, Kraaij M and van den Berg M. Phytochemicals inhibit catechol-O-methyltransferase activity in cytosolic fractions from healthy human mammary tissues: implications for catechol estrogen-induced DNA damage. Toxicol Sci 2004; 81: 316-324.
141.Manach C, Williamson G, Morand C, Scalbert A and Rémésy C. Bioavailability and bioefficacy of polyphenols in humans I. Review of 97 bioavailability studies. Am J Clin Nutr 2005; 81 (suppl): 230S-242S.
142.Manach C, Scalbert A, Morand C, Rémésy C and Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79: 727-747.
143.Harbowy ME and Balentine DA. Tea chemistry. Crit Rev Plant Sci 1997; 16: 415-480.
144.Henning SM, Fajardo-Lira C, Lee HW, Youssefian AA, Go VLW and Heber D. Catechin content of 18 teas and a green tea extract supplement correlated with the antioxidant capacity. Nutr Cancer 2003; 45: 226-235.
145.Yang CS and Landau JM. Effects of tea consumption on nutrition and health. J Nutr 2000; 130: 2409-2412.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔