UFTの悪性脳腫瘍患者におけるpharmacokinetical analysisに関する研究

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UFT, an antitumor agent newly synthesized by Fujii et al., a mixture of FT-207 and uracil in a molar ratio of 1:4, has been noticed to have higher antitumor activity than FT-207 alone. The authors used high performance liquid chromatography to study the pharmacokinetics of UFT after its oral administration (equivalent to 900 mg FT-207) to 3 cases of malignant glioma and 4 cases of metastatic brain tumor. Most of the unmetabolized FT-207, 5-FU, and uracil were excreted in the urine within 24 hrs. The half-life of distribution of FT-207 was 4.59 hrs and its half-life of elimination was 9.99 hrs, while for 5-FU the values were 0.75 hrs and 11.04 hrs, respectively. These results indicated that both FT-207 and 5-FU stayed in plasma for longer periods than when FT-207 alone was used in other studies. In CSF, the concentration of 5-FU was 0.42 μg/ml after 4 hrs and 0.21 μg/g after 6 hrs. Mean concentrations of FT-207, 5-FU, and uracil in malignant glioma tissues were 17.11, 0.20, and 10.12 μg/g, respectively, while in metastatic brain tumor tissues, they were 16.71, 0.47, and 33.57 μg/g, showing that 5-FU and uracil were in higher concentrations in metastatic brain tumor tissues than in malignant glioma tissues. Moreover, concentrations of FT-207 and 5-FU in the tissues adjacent to malignant brain tumor were similarly as high as in the tumor tissues themselves. Thus, UFT maintained high concentrations of 5-FU in plasma, CSF, and tumor tissues. It could be considered that uracil inhibited the degradation of 5-FU. Therefore, UFT showed be expected to show a higher antitumor activity than FT-207 when treating malignant brain tumors.
日本脳神経外科学会の論文
1983-08-15

UFTの悪性脳腫瘍患者におけるpharmacokinetical analysisに関する研究

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