汰癌勝與香砂六君子湯併用之藥物動力學之研究

Pharmacokinetic Interaction of the Xiang-Sha-Liu-Ju-Zu-Tang on Paclitaxel in Rats

Alinafe Magret Kapelemera

Paclitaxel ； 香砂六君子湯 ； 藥物動力學 ； 中西藥交互作用 ； Paclitaxel ； Traditional Chinese Medicine ； Xiang-Sha-Liu-Ju-Zu-Tang ； Pharmacokinetics ； Herb-drug interaction

臺北醫學大學藥學系(碩博士班)學位論文

2017年

碩士

王莉萱

英文

摘要 Paclitaxel是一種天然類萜化合物的抗癌藥，為目前用於乳癌的第一線藥物。癌症患者合並使用中藥情況普遍，根據健保資料庫探勘，香砂六君子湯最常用於緩解Paclitaxel治療過程中產生之副作用。然而化療藥與中藥間是否會因並用而改變彼此之作用，因此本研究之目的為利用藥物動力學模式探討香砂六君子湯合並Paclitaxel之影響。 利用液液萃取為樣品前處理方式與液相層析串聯質譜儀與建立Paclitaxel分析條件後，利用注射Paclitaxel 兩種劑量2 mg/kg、8 mg/kg與Paclitaxel注射前兩個小時口服投與250 mg/kg之香砂六君子湯，比較各組Paclitaxel之藥物動力學參數。結果顯示低劑量2 mg/kg組，先口服香砂六君子湯組別，其血漿中Cmax以及AUC皆較未合並使用中藥顯著下降，分別為0.4倍以及0.65倍 (p < 0.01)。高劑量8 mg/kg Paclitaxel組口服香砂六君子湯，其Cmax顯著下降0.4倍 (p < 0.05)，而AUC則未有顯著改變。香砂六君子湯顯著改變了Paclitaxel之 Cmax 下降可減低毒性，同時不影響8 mg/kg高濃Paclitaxel之功效。因此當Paclitaxel合並使用香砂六君子湯時，仍需注意Paclitaxel之劑量及血漿濃度。 關鍵字: Paclitaxel、香砂六君子湯、藥物動力學、中西藥交互作用

Abstract Paclitaxel is a natural terpenoid compound with anti- cancer activity. It is one of the chemotherapeutic agents used in treatment of solid tumours. In cancer patients, the use of Taditional Chinese Medicine (TCM) is very common. Xiang-Sha-Liu-Ju-Zu-Tang is one of the herbal formulas commonly used among cancer patients to alleviate common side effects. Pharmacokinetic interactions between herbs and chemotherapeutics are very common. The main aim of this study was to investigate the effects of Xiang-Sha-Liu-Ju-Zu-Tang on the pharmacokinetics of paclitaxel. A validated liquid chromatography with tandem mass spectrometry was used to quantify paclitaxel in rats. Pharmacokinetic parameters of paclitaxel were quantified after intravenous administration (2 mg/kg and 8 mg/kg) of paclitaxel to rats in the presence and absence of Xiang-Sha-Liu-Ju-Zu-Tang (250 mg/kg administered 2 h prior to paclitaxel administration). The results indicated a significant decrease in C max and AUC by 0.74 and 0.6 fold respectivily, in plasma concentration of paclitaxel in the pre-treated group co-administered with 2 mg/kg paclitaxel. There was significant decrease in C max by 0.4 fold and no significant change in AUC in the pre-treated group co-administered with 8 mg/kg paclitaxel. Xiang-Sha-Liu-Ju-Zu-Tang significantly affected the pharmacokinetic parameters of paclitaxel 2 mg/kg. Decrease in C max can reduce toxicity while not affecting the efficacy of 8mg/kg paclitaxel. Dosage and plasma concentration of paclitaxel should be considered when paclitaxel is co-administered with Xiang-Sha-Liu-Ju-Zu-Tang. Key words: Paclitaxel; Traditional Chinese Medicine; Xiang-Sha-Liu-Ju-Zu-Tang; Pharmacokinetics; Herb-drug interaction.

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