PubMed1984
5-Fluorouracil(5-FU)is a widely used antitumor agent for treating patients with adenocarcinoma of gastroenterial tract and breast following intravenous or oral administration. The blood level of 5-FU peaked rapidly after intravenous bolus injection and then decreased in a short time, disappearing 90 minutes after injection. But the blood level of 5-FU peaked from 15 to 30 minutes after oral administration of 5-FU tablets or dry syrup and decreased slowly, frequently showing 0.02 microgram/ml at 120 minutes after oral administration. In cancer chemotherapy, a tissue drug concentration is represented by its serum level in practice, generally because of the difficulty in determining the tissue drug level of the patients. This study was performed to determine the tissue 5-FU level after oral administration of 5-FU. Before surgery, 400 to 600 mg of 5-FU tablets was orally administered to 13 patients including 5 cases of gastric, 5 of breast, 1 of colon and 2 of other types of cancer. Tissue specimens of different sites and serum samples were obtained during the operation: cancer tissues, normal gastric or colon wall, normal breast, lymph nodes and subcutaneous fatty tissues, etc. The materials were frozen immediately at -20 degrees C and sent to Pharmaceutical Research Laboratories, Fuji Plant, Kyowa Hakko Kogyo Co., Ltd. ( Nagaizumimachi , Shuntogun , Shizuoka , Japan). The materials were assayed for 5-FU by bioassay method using Staphylococcus aureus 209P or Micrococcus flavus ATCC 10240 as the test organisms. The 5-FU concentration in mastopathy tissue was traced to all of the agents at 20 to 180 minutes after 400 mg of 5-FU was administered orally in tablet form. 5-FU concentrations in gastric cancer tissues ranged from 0.30 to 1.30 micrograms/g at 163 to 235 minutes after administering 600 mg of 5-FU tablets, whereas in normal gastric wall were much lower than in gastric cancer tissues. That in the breast cancer tissues was 0.042 to 0.12 microgram/g at 100 to 240 minutes after oral administration. 5-FU was maintained at a higher concentration in cancer tissues for a long time, while the serum concentration decreased to trace amounts. 5-FU in non-cancerous tissues was invariably traced in most patients as mastopathy tumors. From the above results, 5-FU tablets proved to be a useful drug in cancer chemotherapy.