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

[摘要] References(20)Cited-By(1)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-r3-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 (IC50: 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.

[学科分类] 药理学

[关键词] Emitefur(BOF-A2);5-Fluorouracil-derived drug;Sorivudine (BV-araU);Leukopenia