Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous torasemide in rats.
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.
Lee
Ae K
AK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Kim
Eun J
EJ
Lee
Myung G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004573:Electrolytes / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077786:Torsemide; D014502:Uranyl Nitrate / Q000633:toxicity*
D004232:Diuretics; D004573:Electrolytes; D013449:Sulfonamides; D014502:Uranyl Nitrate; D000077786:Torsemide