Pharmacokinetic changes of cyclosporine after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure

The effects of renal failure on the pharmacokinetics of cyclosporine were investigated after intravenous, 30 mg/kg, and oral, 100 mg/kg, administration of the drug using a rat model of uranyl nitrate-induced acute renal failure (U-ARF). After intravenous administration to rats with U-ARF, the volume of distribution at steady state (1.97 vs. 2.56 1/kg) was significantly smaller, and the area under the blood concentration-time curve (348 vs. 296 mu g h/ml) tended to be greater and total body clearance (0.0851 vs. 0.102 1/h per kg) tended to be slower than those in control rats. After oral administration, the pharmacokinetic parameters were not significantly different between the control rats and rats with U-ARF, suggesting that U-ARF did not considerably affect the pharmacokinetics of cyclosporine after oral administration. (C) 2000 Elsevier Science B.V. All rights reserved.