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

Authors
Citation
Yh. Lee et Ys. Ku, 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, J PHARM PHA, 51(10), 1999, pp. 1149-1154
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
0022-3573 → ACNP
Volume
51
Issue
10
Year of publication
1999
Pages
1149 - 1154
Database
ISI
SICI code
0022-3573(199910)51:10<1149:EOCOTP>2.0.ZU;2-6
Abstract
The effects of cyclosporin on the pharmacokinetics of propranolol have been investigated after intravenous and oral administration of the drugs to con trol rats and to rats with uranyl nitrate-induced acute renal failure. The effects of intravenous cyclosporin, 30 mg kg(-1), on the pharmacokineti cs of intravenous propranolol, 3 mg kg(-1), were significant both in contro l rats and in rats with uranyl nitrate-induced acute renal failure; after i ntravenous administration of cyclosporin plasma concentrations of propranol ol were significantly lower, the area under the plasma concentration-time c urve (AUC) for propranolol from time zero to time infinity was significantl y smaller, and the time-averaged total body clearance of propranolol was si gnificantly 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 fa ilure; after administration of oral cyclosporin plasma concentrations of pr opranolol were significantly higher and the AUC of propranolol was signific antly greater. These data suggest that cyclosporin increases the elimination of propranolo l, and that the first-pass effects of propranolol are reduced, or gastroint estinal absorption of propranolol is increased, or both, by cyclosporin.