[Metabolic characteristics and antitumor activity of BOF-A2, a new 5-fluorouracil derivative].
A new 5-fluorouracil (5-FU) derivative, BOF-A2 (3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1- ethoxymethyl- 5-fluorouracil), is consisted of EM-FU (1-ethoxymethyl-5-fluorouracil) which is specifically and gradually converted to 5-FU by the drug-metabolizing enzyme of liver microsomes and CNDP (3-cyano-2,6-dihydroxypyridine), a potent inhibitor of 5-FU degradation in the liver. When BOF-A2 was given orally, blood levels of the main metabolites, EM-FU and CNDP, were maintained for a longer time in the tumor-bearing rats, and eventually the blood 5-FU levels were maintained over 12 hours. Moreover, 5-FU levels in the tumor tissue tended to be maintained higher and longer time over 24 hrs. than those in the blood of rats. Antitumor activity of such characterized BOF-A2 was investigated with transplantable tumors in rodents and DMBA-induced breast carcinomas in rats. The ED 50 (the dose for 50% inhibition of tumor growth) value was about 15 to 25 mg/kg against the tumors tested. These result may suggest that BOF-A2 has potent antitumor activity in accordance to the long persistence of 5-FU level in the tumor tissue.
Shirasaka
T
T
Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga.
Fukushima
M
M
Shimamoto
Y
Y
Kimura
Y
Y
Ohshimo
H
H
Imaoka
T
T
Kimura
A
A
Utsunomiya
T
T
Fujii
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051381:Rats
D000970:Antineoplastic Agents; C059823:1-ethoxymethyl-5-fluorouracil; C053194:Emitefur; D005472:Fluorouracil