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

Abstract

The effects of cyclosporin on the pharmacokinetics of propranolol have been investigated after intravenous and oral administration of the drugs to control rats and to rats with uranyl nitrate-induced acute renal failure. The effects of intravenous cyclosporin, 30 mg kg(-1), on the pharmacokinetics of intravenous propranolol, 3 mg kg(-1), were significant both in control rats and in rats with uranyl nitrate-induced acute renal failure; after intravenous administration of cyclosporin plasma concentrations of propranolol were significantly lower, the area under the plasma concentration-time curve (AUC) for propranolol from time zero to time infinity was significantly smaller, and the time-averaged total body clearance of propranolol was significantly faster. The effects of oral cyclosporin, 100 mg kg(-1), on the pharmacokinetics of oral propranolol, 10 mg kg(-1), were also significant, both in control rats and in rats with uranyl nitrate-induced acute renal failure; after administration of oral cyclosporin plasma concentrations of propranolol were significantly higher and the AUC of propranolol was significantly greater. These data suggest that cyclosporin increases the elimination of propranolol, and that the first-pass effects of propranolol are reduced, or gastrointestinal absorption of propranolol is increased, or both, by cyclosporin.