維他命E包含四種tocopherols及四種tocotrienols，主要的功能為脂溶性的抗氧化劑。而Vitamin E TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate)，為維他命E的衍生物，可作為吸收促進劑(absorption enhancer)，而於臨床上可用來治療維他命E吸收不良相關疾病。通常觀察Vitamin E TPGS在臨床上的療效,都以血中α-tocopherol的濃度做為指標，因Vitamin E TPGS會在體內酯解為α-tocopherol。但文獻中對Vitamin E TPGS分析方法及其藥動研究極少，且最近有研究顯示，維他命E的代謝可能與CYP3A有關。所以Vitamin E TPGS如當作CYP3A相關藥物的賦形劑，其中的excipients-drug interaction就值得注意，而維他命E與藥物的drug-drug interaction亦值得進一步探討。

　　本研究的目的為開發一簡單、快速及靈敏定量之分析方法並實際應用至血漿中Vitamin E TPGS及α-tocopherol之濃度分析；研究Vitamin E TPGS及α-tocopherol於老鼠活體內之動態；口服不同天數的Vitamin E TPGS，以體外及體內實驗(in vitro-in vivo)評估其對肝臟酵素CYP3A的誘導效應。

　　實驗研究結果已開發一分析方法，經確效後實際應用至Vitamin E TPGS及α-tocopherol之血漿濃度分析與藥動學實驗。在老鼠體內Vitamin E TPGS與α-tocopherol之動態有劑量依性關係。而Vitamin E TPGS在正常老鼠的口服生體可用率為0.59。體外實驗顯示，經投予老鼠不同天數的Vitamin E TPGS，其肝臟CYP3A酵素含量有增加的趨勢，然而並未有顯著統計差異。且以CYP3A探針cisapride當作體內評估CYP3A的活性，發現其清除率在實驗組及對照組並沒有統計上的差異。

　　本研究的結論為Vitamin E TPGS長期服用時，其分解產生的α-tocopherol可能不會對肝臟CYP3A有誘導的效果。

　　Introduction. Vitamin E includes four tocopherols and four tocoptrienols, which are major lipid-soluble antioxidants in vivo. Vitamin E TPGS, D-α-tocopheryl polyethylene glycol 1000 succinate, is a derivative of vitamin E. It has been introduced in pharmaceuticals as an absorption enhancer. Clinically, administration of Vitamin E TPGS is the treatment of choice in vitamin E deficiency. However, there are no reports on the pharmacokinetics and analysis of Vitamin E TPGS so far. Recent reports of CYP3A involvement in vitamin E metabolism has attracted more attention on the potential Vitamin E TPGS related excipient-drug interactions, as many drugs are metabolized by CYP3A.

　　Objectives. The aims of this study are to develop a simple, rapid, and sensitive high-performance liquid chromatography (HPLC) method to quantitate the concentration of Vitamin E TPGS and α-tocopherol in plasma; to investigate the pharmacokinetics of Vitamin E TPGS and α-tocopherol in rats; and to evaluate the induction effects of Vitamin E TPGS on hepatic CYP3A isozymes.

　　Results. A new validated HPLC method for the simultaneous analysis of Vitamin E TPGS and α-tocopherol in plasma was developed, and was applied successfully to pharmacokinetic studies. The disposition of Vitamin E TPGS and α-tocopherol in rats displayed dose-dependent characteristics. The oral bioavailability of Vitamin E TPGS in normal rats is about 0.59. Chronic administration of Vitamin E TPGS showed a trend of increasing amount of CYP3A in rats, however, without statistical significance; Furthermore, when cisapride was used to assess hepatic CYP3A activity in-vivo, the clearance of cisapride remained unchanged following 14 days administration of Vitamin E TPGS in rats.

　　Conclusion. Chronic administration of Vitamin E TPGS at therapeutical doses does not have significant induction effects on hepatic CYP3A enzymes.

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