A comparative study on the cardiotoxicity of 5-fluorouracil and ftorafur in rabbits.

Abstract

Intravenous administration of 5-FU 15 mg/kg significantly lowered the blood pressure 17 hours after, while ftorafur 20 mg/kg did not alter the pressure. Ftorafur 60 mg/kg significantly lowered the pressure 17 hours after the drug administration. In a large number of rabbits treated with 5-FU 15 mg/kg or ftorafur 60 mg/kg, the ventricular fibrillation spontaneously produced within 17 hours after the treatment. Adrenaline 5-50 μg/kg was injected into an ear vein in a stepwise manner, to assess whether or not the drug would induce a ventricular fibrillation. Pretreatment with 5-FU 15 mg/kg sensitized the ventricle to adrenaline-induced ventricular fibrillation, while ftorafur 20 and 60 mg/kg did not. The time required to produce ventricular fibrillation after a large dose (200 μg/kg) of ouabain was significantly shorter in 5-FU 15 mg/kg and ftorafur 60 mg/kg treated (17 hours before) groups than in the control group, while in the ftorafur 20 mg/kg treated group, the time was much the same as seen in the control group. These findings indicate that the cardiotoxicity of ftorafur in rabbits may be weaker than that of 5-FU.