Pharmacodynamics of Co-Administration of Uracil and 1-(2-Tetrahydrofuryl)-5-Fluorouracil (FT-207) for Malignant Brain Tumors

UFT, a mixture of FT-207 and uracil in a molar ratio 1 : 4, has been noticed to have the higher antitumor activity to various tumors other than FT-207. We studied the pharmacodynamics of UFT (900 mg for FT-207) after oral administration on 3 cases of malignant glioma and 4 cases of metastatic brain tumor by using high performance liquid chromatography, and the following results obtained;

1. Most of unchanged FT-207, 5-FU and uracil were excreted in the urine within 24 hours.

2. The t1/2 of α-phase of FT-207 was 4.59 hours and that of β-phase was 9.99 hours. The t1/2 ofα-phase of 5-FT was 0.75 hours, and that ofβ-phase was 11.04 hours. The AUC of 5-FU was 12.434 µg· hrs/ml. This drug was found to stay in the plasma over a long period, followed by a slow elimination. In CSF, the higher concentration of 5-FU stayed over a longer period.

3. The concentration of FT-207 in the brain tumor tissues was 17.11 µg/g on the average in malignant glioma and 17.61 µg/g on the average in metastatic brain tumor. The concentration of 5-FU was 0.02 µg/g on the average in the former, and 0.47 µg/g on the average in the latter, which indicating an efficient transfer to the tissues of metastatic brain tumor. The concentration of FT-207 and 5-FU in the brain tissues adjacent to the tumor was approximately the same as that in the brain tumor tissues, indicating an effective transfer to the brain tissues adjacent to the tumor.

4. On the basis of the results of this study, uracil seems to inhibit the degradation of 5-FU in the liver and/or in the tumor tissues themselves, and to enhance the concentration of 5-FU in the brain tumor tissues and the brain tissues adjacent to the tumor. UFT would be useful as a chemotherapeutic agent agent for malignant brain tumors.