Cellular pharmacology of fluorinated pyrimidines in vivo in man.
Cellular pharmacology of fluorinated pyrimidines in vivo in man.
复制标题
氟化嘧啶在人体内的细胞药理学。
DOI：
10.1007/bf00178188
复制
发表时间：
1989
影响因子：
3.4
通讯作者：
BeartJr,RW
中科院分区：
文献类型：
--
作者：
Kovach,JS;BeartJr,RW
氟化嘧啶，特别是 5-氟尿嘧啶 (FUra)，自 Charles Heidelberger 博士于 1950 年代末开发以来一直是密集且几乎连续的基础和临床研究的主题。尽管付出了如此巨大的努力，FUra 影响个体癌症患者肿瘤生长的最重要机制以及该药物单独给药以及与其他药物或电离辐射联合给药的治疗最佳方法仍然是人们感兴趣的问题。本文回顾了与以下论文相关的 FUra 研究的各个方面：对于该药物以及用于治疗人类癌症的其他药物，如果要实现个体化治疗的合理基础，则需要药物和代谢物的细胞内浓度作为剂量、给药方案和时间的函数的数据，以与对肿瘤增殖的影响相关。对快速注射和 24 小时输注放射性标记药理活性剂量的 FUra 后，人类结直肠癌和邻近正常肠中 FUra 和代谢物的组织浓度正在进行的研究进行了初步描述，作为了解更多氟化嘧啶细胞药理学的一种方法。
Fluorinated pyrimidines, particularly 5-fluorouracil (FUra), have been the subject of intense and almost continuous basic and clinical study since development in the late 1950's by Dr. Charles Heidelberger. Despite this intensive effort, the most important mechanisms by which FUra influences tumor growth in individual cancer patients and the therapeutically optimum method of administration of the drug alone and in combination with other drugs or ionizing radiation continue to be questions of interest. This article reviews aspects of the study of FUra pertinent to the thesis that for this drug as for other agents used to treat human cancers, data on intracellular concentrations of drug and metabolites as a function of dose, schedule of administration and time are needed for correlation with effects on tumor proliferation if a rational basis for individualization of therapy is to be achieved. A preliminary description of ongoing studies of the tissue concentrations of FUra and metabolites in human colorectal carcinoma and in adjacent normal bowel after rapid injection and after 24-hour infusion of radiolabelled pharmacologically active doses of FUra is included as one approach to learning more about the cellular pharmacology of fluorinated pyrimidines.