Disposition of Vitamin E TPGS in Rats and Its Effect on CYP3A Drug Metabolism

• Main Authors: Meng-Chun Ho, 何孟漘
• Other Authors: Chen-Hsi Chou
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/55904619031212145004

碩士 === 國立成功大學 === 臨床藥學研究所 === 92 === 　　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.