Effects of propranolol on the pharmacokinetics of cyclosporine after intravenous and oral administration to control rats and rats with uranyl nitrate-induced acute renal failure

Abstract

Effects of propranolol on the pharmacokinetics of cyclosporine were investigated after intravenous and oral administration of the drugs to control rats and rats with uranyl nitrate-induced acute renal failure (U- ARF). Effects of intravenous propranolol, 3 mg/kg, on the pharmacokinetics of intravenous cyclosporine, 3 and 30 mg/kg, to control rats, and 30 mg/kg, to rats with U-ARF seemed to be negligible. However, the effects of orally administered propranolol, 10 mg/kg, on the area under the blood concentration-time curve (AUC) of oral cyclosporine were significant after oral administration of cyclosporine, 10 and 100 mg/kg, to control rats. For example, the AUC of cyclosporine increased significantly (33.1 versus 24.7 μg h/ml) at cyclosporine oral dose of 10 mg/kg, however, the value decreased significantly (167 versus 235 μg h/ml) at cyclosporine oral dose of 100 mg/kg. Effects of orally administered propranolol, 10 mg/kg, on the pharmacokinetics of orally administered cyclosporine, 100 mg/kg, seemed to be negligible in rats with U-ARF.