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首页> 外文期刊>薬物動態 >Pharmacokinetics of capecitabine,of triple-prodrug of 5-fu:usefulness of physiologically based pharmacokinetic model for quantitative understanding of tumor-selective distribution of 5-fu after oral administration of the triple-prodrug
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Pharmacokinetics of capecitabine,of triple-prodrug of 5-fu:usefulness of physiologically based pharmacokinetic model for quantitative understanding of tumor-selective distribution of 5-fu after oral administration of the triple-prodrug

机译：5-Pue三宝三宝石的药代动力学：在口服三宝口服施用5-FU肿瘤选择性分布定量理解的生理基于药代动力学模型的有用性

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摘要

Capecitabine,an orally administered triple prodrug of 5-FU shows tumor-preferential exposure of 5-FU by being sequentially metabolized to 5-FU by three enzymes,which show relatively specific orgn expression.To investigate the mechanism of tumor-preferential exposure of 5-FU after oral administration of capecitabine,a physiologically based pharmacokinetic model describing the pharmacokinetic behaviors of capecitabine,a physiologically based pharmacokinetic modeldecribing the pharmacokinetic behaviors of capecitabine and its metabolites including 5-FU in humans was constructed.The factors that have the greatest influence on the pharmacokinetics of 5-FU after administration of capecitabine were clarified by sensitivity analyses.The sensitivity analysis demonstrated the exposure of tumor tissue to 5-FU depends mainly on the activity of both thymidine phosphorylase(producing enzyme of 5-FU from the precursor,5"-DFUR)and DPD(eliminating enzyme of 5-FU)in tumor tissue,as well as blood flow rate in tumor tissue with saturation of DPD activity resulting in higher 5-FU AUC in tumor tissue.The therapeutic index of capecitabine was found to be at least 17 times greater than that of other fluoropyrimidine,including doxifluridine,the pfodrug of 5-FU,and 5-FU over their respective clinical dose ranges.
机译：Capecitabine，一种口服给药的三重前药，5-FU显示出5-FU的肿瘤优先暴露，通过三种酶被依次代谢到5-FU，其显示出相对特异性的ORGN表达。研究肿瘤优先暴露的5个机制5 -Fu在杂志施用亚己酮后，构建了一种物理上基于能源基础的药代动力学的药代动力学的药代动力学模型，其基于生理基础的药代动力学的药代动力学性能的癸二符和其代谢产物，包括5-FU在人类中。对其产生最大影响的因素通过敏感性分析阐明了杂志中的5-fu的药代动力学。敏感性分析阐明了肿瘤组织至5-fu的暴露主要取决于胸苷磷酸化酶的活性（来自前体的5-FU的酶，5肿瘤组织中的“-dfur）和DPD（消除5-FU）以及血流Ra Te在肿瘤组织中，具有DPD活性的饱和，导致肿瘤组织中的5-FU AUC。发现亚锡三滨的治疗指数比其他氟嘧啶，包括Doxiflurimidine，5-Fu的含量为5倍，它们各自的临床剂量范围内的5-FU。

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  • 来源
    《薬物動態》 |2001年第suppla期|共2页
  • 作者

    Yuichi Sugiyama; Yuko Tsukamoto; Ikuo Horll;

  • 作者单位

    The University of Tokyo Graduate School of Pharmaceutical Sciencess Department of Molecular Pharmacokinetics;

    Nippon Roche Research Center Department of Preclinical Science;

    Nippon Roche Research Center Department of Preclinical Science;

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  • 原文格式 PDF
  • 正文语种 jpn
  • 中图分类 药学;制药化学工业;
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