Safety of torasemide in healthy adult dogs administered daily for 26 weeks

Abstract

Thirty-two (16 males and 16 females) healthy young beagles were randomly divided into four groups of eight. The control group remained untreated. Torasemide (ISEMID^® , Ceva Santé Animale) was orally administered, once daily, at 0.5 mg/kg from Days 1-5 then 0.25 mg/kg to Day 182, and at three times and five times this dosing regimen in two additional groups. Treated animals (predominantly at the higher dose levels) showed dryness of the oral mucosa, evidence of diuresis, decreased diet consumption, decreased bodyweight gain over the first 3 weeks, increased water consumption, increases in erythrocytes count, haemoglobin, calcium and magnesium, decrease in chloride, phosphorus, potassium and sodium, increases in urine pH, decreases in urine specific gravity and increases in serum aldosterone concentrations. Plasma concentrations of torasemide increased in a dose-dependent manner and showed no evidence of accumulation. There were also changes to electrocardiogram patterns and the macroscopic and microscopic appearance of the kidney and adrenal glands, but these changes were almost exclusively confined to the over-dosed groups. In conclusion, torasemide was found to be safe when administered to dogs at 0.25 mg/kg once daily for 26 weeks, and any changes were consistent with its known diuretic effects.

Keywords: canine; cardiovascular disease; loop diuretic; torasemide.

FIGURE 1

Mean and SEM bodyweight gain for male animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). * p< .05, ** p< .01

FIGURE 2

Mean and SEM bodyweight gain for female animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). * p< .05, ** p< .01

FIGURE 3

Mean and SEM water consumption for male animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). Data collected on Days 191 and 205 were from a single recovery animal for each group and are therefore not mean values. * p< .05, ** p< .01

FIGURE 4

Mean and SEM water consumption for female animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). Data collected on Days 191 and 205 were from a single recovery animal for each group and are therefore not mean values. * p< .05, ** p< .01

FIGURE 5

Mean and SEM serum aldosterone concentration measurements for male animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). Data collected on Day 210 were from a single recovery animal for each group and are therefore not mean values. * p< .05, ** p< .01

FIGURE 6

Mean and SEM serum aldosterone concentration measurements for female animals (n = 4 per group) during the study. Torasemide was administered once daily on Day 1 to Day 5 (at double the maintenance dose) and Days 6 to 182 (at a maintenance dose of 0.25 mg/kg (1X), 0.75mg/kg (3X) and 1.25 mg/kg [5X]). Data collected on Day 210 were from a single recovery animal for each group and are therefore not mean values. * p< .05