Leukopenia-Inducing Effect of a Combination of a New 5-Fluorouracil (5-FU)-Derived Drug, BOF-A2 (Emitefur), with Other 5-FU-Derived Drugs or BV-araU (Sorivudine) in Rats

• Published in: Japanese Journal of Pharmacology 1996, Vol.70 (2), p.139-148
• Main Authors: shun Miyauchi, Takeshi Imaoka, Tadashi Okada, Masaaki Motoyama, Teruhisa Kawaguchi, Hitoshi Akiyama, Masaaki Odomi
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

BOF-A2 (emitefur：3-{3-[6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl]benzoyl}-1-ethoxymethyl-5-fluorouracil), a novel 5-FU (5-fluorouracil)-derived drug, was co-administered with other conventional 5-FU-derived drugs or BV-araU [sorivudine：1-β-D-arabinofuranosyl-(E)-5-(2-bromovinyluracil)] for 8 consecutive days to rats. BOF-A2 (6 or 8 mg/kg, p.o.) co-administered with other 5-FU-derived drugs elevated the plasma 5-FU concentration 3-to 23.3-fold and decreased the peripheral white blood cell (WBC). The percentage decreases of WBC by 5-FU (4 mg/kg, i.p.), UFT (16 mg/kg, p.o.), tegafur (FT; 16 mg/kg, p.o.), carmofur (HCFU; 15 mg/kg, p.o.), doxifluridine (5'-DFUR; 16 mg/kg, p.o.) and flucytosine (200 mg/kg, p.o.) were 25.7%, 31.9%, 70.3%, 32.0%, 58.6% and 30.0%, respectively, compared with each drug alone. On the other hand, these phenomena did not occur with BV-araU. These findings can be attributed to the fact that the inhibitory activity of CNDP (3-cyano-2,6-dihydroxypyridine) for 5-FU degradation (IC_50 ：6.3×10^-9 M) is potent and 6000 times greater than that of BVU [(E)-5-(2-bromovinyl) uracil], another inhibitor of 5-FU degradation.