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

Abstract

ABSTRACT-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:for 8 con secutive 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 .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 at tributed to the fact that the inhibitory activity of CNDP (3-cyano-2,6-dihydroxypyridine)for 5-FU degra dation (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.

Hemato-Protective Effects Of Ocimum Gratissimum Leaves Aqueous Extract In Adult Male Wistar Rats

“…Intraperitoneally injection of 20mg/kg body weight of 5-Flourourasilday for 2 weeks induced leukopenia in line with the procedures of Shun et al, (1996) and Jain, (1986) [19]. By this method, leukopenia was induced and confirmed (by WBC count) in animals prior to feeding with O. Gratissimum extract.…”

“…Repetitive doses of phenylhydrazine was administered to the animals in line with the methods of Crosby and Conrad, (1960) in order to induce haemolytic anaemia [18]. Blood sample collection was carried out at various times while examining the fragility profile and osmotic resistance.…”

Possible drug–drug interaction in dogs and cats resulted from alteration in drug metabolism: A mini review

“…In 1993, many patients with cancer and herpes zoster, a viral disease, were died from interactions of an antiviral (sorivudine) with anticancer prodrug, 5-fluorouracil. This was due to the inactivation of an enzyme catalyzing the metabolism of 5-fluorouracil by co-administration of sorivudine [5–7] . Since the abovementioned medical accidents, researchers have paid much attention to pharmacokinetic drug–drug interaction originated from the alteration in drug metabolism in human medicine.…”