Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous torasemide in rats.

Abstract

Pharmacokinetic and pharmacodynamic parameters were evaluated after an intravenous administration of torasemide at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (U-ARF). In rats with U-ARF, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (6380 versus 4450 microg min/ml) than that in control rats. This was due to significantly faster total body clearance (1.57 versus 2.25 ml/min/kg) in the rats. The faster total body clearance in rats with U-ARF could be due to significantly faster nonrenal clearance (1.51 versus 2.22 ml/min/kg due to faster metabolism) since renal clearance (0.0365 versus 0.00199 ml/min/kg) was significantly slower (due to impaired kidney function) than that in control rats. The 8-h urine output was significantly smaller in rats with U-ARF (178 versus 22.0 ml/kg), however, the 8-h urinary excretion of sodium, potassium, and chloride were not significantly different between two groups of rats.