Oral administration of BOF-A2 to rats with lung transplanted tumors results in increased 5-fluorouracil levels.
A new tumor model was developed in which solid Yoshida sarcoma tissue injected intravenously developed into tumors in the lungs of about 30% (13/42) of the inoculated rats. Histological examination revealed that alveoli were occupied with tumor cells and the tumors were similar to those obtained by subcutaneous inoculation. Using this model, the concentrations of 5-fluorouracil (5-FU) in tumor tissue 12 h after oral administration of 3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)-benzoyl]-1-ethoxy methyl- 5-fluorouracil (BOF-A2, 36 mumol/kg) or a combination of tegafur and uracil in a molar ratio 1 to 4 (UFT, 50 mumol/kg) were found to be 129.8 ng/g and 19.2 ng/g, respectively. Thus, compared to treatment with UFT, BOF-A2 resulted in higher levels of 5-FU in lung tumor tissues. Increased concentrations of 5-FU should have a superior anti-tumor effect and so BOF-A2 merits clinical trial in the treatment of patients with lung cancer.
Miyauchi
S
S
Fujii Memorial Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga.
Imaoka
T
T
Utsunomiya
T
T
Hayashi
K
K
Kubo
M
M
Kawaguchi
T
T
Matsui
Y
Y
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004347:Drug Interactions; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D011725:Pyridines / Q000097:blood; D051381:Rats; D012517:Sarcoma, Yoshida / Q000378:metabolism*; D005641:Tegafur / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014498:Uracil / Q000494:pharmacology
D000970:Antineoplastic Agents; D004338:Drug Combinations; D011725:Pyridines; D005641:Tegafur; C053195:2,6-dihydroxy-3-cyanopyridine; D014498:Uracil; C059823:1-ethoxymethyl-5-fluorouracil; C053194:Emitefur; D005472:Fluorouracil