Miyauchi S, Imaoka T, Okada T, Motoyama M, Kawaguchi T, Akiyama H, Odomi M
Fujii Memorial Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan.
Jpn J Pharmacol. 1996 Feb;70(2):139-48. doi: 10.1254/jjp.70.139.
BOF-A2 (emitefur: 3-(3-[6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl]benzoyl)-1-ethoxy- methyl-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-beta-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 x 10(-9) M) is potent and 6000 times greater than that of BVU [(E)-5-(2-bromovinyl) uracil], another inhibitor of 5-FU degradation.
BOF - A2（依米替氟：3 - (3 - [6 - 苯甲酰氧基 - 3 - 氰基 - 2 - 吡啶氧基羰基]苯甲酰基) - 1 - 乙氧基甲基 - 5 - 氟尿嘧啶），一种新型的5 - FU（5 - 氟尿嘧啶）衍生药物，与其他传统的5 - FU衍生药物或BV - araU [索立夫定：1 - β - D - 阿拉伯呋喃糖基 - (E) - 5 - (2 - 溴乙烯基尿嘧啶)]连续8天共同给予大鼠。BOF - A2（6或8毫克/千克，口服）与其他5 - FU衍生药物共同给药可使血浆5 - FU浓度升高3至23.3倍，并使外周白细胞（WBC）减少。与单独使用每种药物相比，5 - FU（4毫克/千克，腹腔注射）、优福定（16毫克/千克，口服）、替加氟（FT；16毫克/千克，口服）、卡莫氟（HCFU；15毫克/千克，口服）、去氧氟尿苷（5'-DFUR；16毫克/千克，口服）和氟胞嘧啶（200毫克/千克，口服）导致的WBC百分比下降分别为25.7%、31.9%、70.3%、32.0%、58.6%和30.0%。另一方面，BV - araU未出现这些现象。这些发现可归因于CNDP（3 - 氰基 - 2,6 - 二羟基吡啶）对5 - FU降解的抑制活性（IC50：6.3×10(-9) M）很强，比另一种5 - FU降解抑制剂BVU [ (E) - 5 - (2 - 溴乙烯基)尿嘧啶]高6000倍。
