臺灣博碩士論文加值系統

Paclitaxel 為一具有強力抗腫瘤活性之藥物，臨床上常以靜脈注射給
藥，用於治療乳癌、卵巢癌及肺癌。Paclitaxel 由CYP 2C8 及3A4 代謝，並且為P-gp 親和力高之受質，有71 % 的原型及其代謝物會從糞便途徑排出。豆漿是在亞洲國家常見且重要的飲品，含有大豆異黃酮如daidzin,genistin, daidzein 及 genistein。在先前的研究發現，大豆異黃酮可能會增加P-gp 活性，其代謝物可能會增加CYP 3A4 活性。近年來有文獻提出大豆發酵製成的萃取液有助於減緩化療藥所引起的副作用，但機制未明。故本研究擬以大鼠為動物模型，初步探討口服豆漿後，是否會改變靜脈給藥paclitaxel 在體內的動力學行為。
本研究先行開發以HPLC-UV 方法，定量豆漿粉中daidzin、genistin、
daidzein 及genistein。並續以大鼠作為動物模型進行預試驗。分別餵予大鼠水及高、低劑量之豆漿後，由靜脈給予paclitaxel，於特定時間抽血，並且以HPLC 方法進行定量。
初步結果顯示，大鼠在口服豆漿後，靜脈注射的paclitaxel 血藥曲線
下面積下降。此一現象將有進一步評估的空間。

Paclitaxel is one of the most promising antineoplastic agents and usually administered intravenously for the treatments of a variety of cancers such as breast, ovarian and lung cancers. Paclitaxel is metabolized by cytochrome P 450 (CYP) 2C8 and 3A4. Paclitaxel is a substrate of P-glycoprotein (P-gp) with high affinity. 71% of paclitaxel and its metabolites are excreted into
feces. Soymilk, a common beverage of Asian people, contains plenty of isoflavones such as daidzin, genistin, daidzein and genistein. Previous studies reported that soy isoflavones activated the function of P-gp and their
metabolites induced the activity of CYP 3A4. Another study has demonstrated that the fermented soy extract could improve the chemotherapy-induced side effects. However, the mechanism is unknown. Therefore, this study aimed to investigate the effect of soymilk on the pharmacokinetics of intravenous paclitaxel.
HPLC-UV assay was carried out first for quantifying daidzin, genistin, daidzein, and genistein in soymilk powder. In preliminary experimental animal study, rats were orally given water or two dosages of soymilk and
injected paclitaxel intravenously. Blood samples were withdrawn at predetermined time points, and the paclitaxel concentrations in plasma were determined by HPLC method.
The primary results showed that soymilk significantly decreased the systemic exposure of intravenous paclitaxel. Further investigation will be
required to identify the mechanism.

目錄……………………………………………………………………. Ⅰ
附圖目錄………………………………………………………………. Ⅲ
附表目錄………………………………………………………………. Ⅳ
中文摘要………………………………………………………………. Ⅵ
英文摘要………………………………………………………………. Ⅶ
第一章 緒論…………………………………………………………... 1
第二章 總論…………………………………………………………... 8
第一節 大豆簡介…………………………………………........... 8
第二節 Paclitaxel簡介…………………………………............... 16
第三節 轉運蛋白之簡介…………………………………..……. 21
第四節 細胞色素 P450之簡介……………………………........ 27
第三章 材料與方法…………………………………......................... 29
第一節 實驗材料……………………………................................. 29
一、 標準品與試劑…………………………………................. 29
二、 儀器設備…………………………………......................... 30
三、 實驗動物…………………………………......................... 32
第二節 實驗方法…………………………………....................... 33
(一) 豆漿粉中daidzin、genistin、daidzein、genistein之定量….. 33
(二) 豆漿於大鼠體內對靜脈注射paclitaxel之動力學影響初探…………………………………………………….........
36
第四章 實驗結果與討論……………………………......................... 41
第一節 豆漿粉中daidzin、genistin、daidzein、genistein之定量………………………………………………………...
41
第二節 豆漿於大鼠體內對靜脈注射paclitaxel之動力學影響初探………………………………………………….......
43
第五章 結論…………………………………..................................... 49
第六章 參考文獻…………………………………............................. 50
附圖……………………………………………………………………. 60
附表……………………………………………………………………. 63

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