Effect of Dipyrone on the Renal Clearance and Urinary Excretion of Norfloxacin in Sheep

The effect of dipyrone on the renal clearance and urinary excretion of norfloxacin was investigated in eight healthy female sheep. In each animal, after a single intramuscular administration of norfloxacin, 5 mg/kg body weight, a wash out period of seven days was given. Afterwards, norfloxacin was administered with dipyrone as concurrent intramuscular injection, 50 mg/kg body weight. Following a single and concurrent drug administration, blood and urine samples were collected at different time intervals and analyzed for norfloxacin and creatinine concentrations. The value of diuresis after single administration of norfloxacin was 0.023 ± 0.004 ml/min.kg, while following concurrent administration with dipyrone it was 0.014 ± 0.02 ml/min.kg. Mean values for renal clearance of creatinine following single and concurrent administration with dipyrone were 0.042 ± 0.005 and 0.027 ± 0.003 ml/min.kg, respectively, while respective values for renal clearance of norfloxacin were 0.013 ± 0.002 and 0.008 ± 0.001 ml/min.kg. The renal handling of norfloxacin involved active tubular secretion following its administration alone or with dipyrone. The ratio between the renal clearance of norfloxacin and dipyrone remained less than one after the administration of norfloxacin alone and concurrently with dipyrone, which was indicative of back diffusion of the drug. The mean values for the cumulative percent of dose norfloxacin excreted at 12 hours following administration of norfloxacin alone was 1.86 ± 0.05 and following its concurrent administration with dipyrone was 1.35 ± 0.05. Thus, it is evident that besides glomerular filtration, renal handling of norfloxacin also involved back diffusion and active tubular secretion. It was concluded that these mechanisms showed no change in sheep following norfloxacin administration with dipyrone. However, dipyrone reduced GFR inducing less urinary excretion of norfloxacin.