國家衛生研究院 NHRI:Item 3990099045/3077
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    题名: Enhanced oral bioavailability of paclitaxel by D-alpha-tocopheryl polyethylene glycol 400 succinate in mice
    其它题名: Enhanced oral bioavailability of paclitaxel by d-α-tocopheryl polyethylene glycol 400 succinate in mice
    作者: Ho, PY;Yeh, TK;Yao, HT;Lin, HL;Wu, HY;Lo, YK;Chang, YW;Chiang, TH;Wu, SHW;Chao, YS;Chen, CT
    贡献者: Division of Biotechnology and Pharmaceutical Research
    摘要: Paclitaxel is widely used to treat several types of solid tumors. The commercially available paclitaxel formulation contains Cremophor/ethanol as solubilizers. This study evaluated the effects of D-alpha-tocopheryl polyethylene glycol 400 succinate (TPGS 400) on the oral absorption of paclitaxel in mice. Mice were given an intravenous (18 mg/kg) or oral (100 mg/kg) dose of paclitaxel solubilized in Cremophor/ethanol or in TPGS 400/ethanol formulations. Paclitaxel plasma concentrations and pharmacokinetic parameters were determined. The maximal plasma concentrations of paclitaxel after an oral dose were 1.77 +/- 0.17 and 3.39 +/- 0.49 mu g/ml for Cremophor/ethanol and TPGS 400/ethanol formulations, respectively, with a similar time at 40-47 min to reach the maximal plasma concentrations. The oral bioavailability of paclitaxel in TPGS 400/ethanol (7.8%) was 3-fold higher than that in Cremophor/ethanol (2.5%). On the other hand, the plasma pharmacokinetic profiles of intravenous paclitaxel demonstrated a superimposition for the two formulations. Furthermore, TPGS 400 concentration-dependently increased the intracellular retention of Rhodamine 123 in Caco-2 cells and enhanced paclitaxel permeability in monolayer Caco-2 cultures. TPGS 400 at concentrations up to 1 mM did not inhibit testosterone 6 beta-hydroxylase, a cytochrome P450 isozyme 3A in liver microsomes metabolizing paclitaxel. Our results indicated that TPGS 400 enhances the oral bioavailability of paclitaxel in mice and the enhancement may result from an increase in intestinal absorption of paclitaxel.
    关键词: Pharmacology & Pharmacy
    日期: 2008-07-09
    關聯: International Journal of Pharmaceutics. 2008 Jul;359(1-2):174-181.
    Link to: http://dx.doi.org/10.1016/j.ijpharm.2008.04.013
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0378-5173&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000257530400022
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=44749086490
    显示于类别:[陳炯東] 期刊論文
    [趙宇生(2002-2013)] 期刊論文
    [葉燈光] 期刊論文

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