Chronic cyclosporine administration induces renal P-glycoprotein in rats

European Journal of Pharmacology
J Liu, L J Brunner

Abstract

The effect of cyclosporine doses on renal P-glycoprotein expression was examined. Rats were given cyclosporine orally at 2, 10, 30 mg/kg/day or subcutaneously at 1, 5, 15 mg/kg/day for 28 days with or without 14 days of additional vehicle dosing. Following cyclosporine dosing, renal function and P-glycoprotein expression were measured. Renal function was reduced in rats receiving oral cyclosporine and the highest subcutaneous dose, 15 mg/kg/day. Western blot analysis showed that cyclosporine administered orally at 10 and 30 mg/kg/day and subcutaneously at 15 mg/kg/day induced significantly renal P-glycoprotein expression. After discontinuation of cyclosporine, renal P-glycoprotein returned to pre-dosing levels in oral groups, whereas the return was incomplete in subcutaneous groups. These results indicate that cyclosporine induces renal P-glycoprotein overexpression a dose-dependent manner.

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Citations

Mar 24, 2007·Pharmaceutical Research·Ignacio OrtegaRosario Calvo
May 29, 2013·International Journal of Pharmaceutics·Noël KnopsDirk Kuypers
Jan 22, 2003·Advanced Drug Delivery Reviews·Jiunn H Lin
May 13, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Núria LloberasJosep M Grinyó
Dec 20, 2002·Clinical Pharmacokinetics·Jiunn H Lin, Masayo Yamazaki
Nov 12, 2010·Expert Opinion on Drug Metabolism & Toxicology·Clemence TariraiJosias H Hamman
Apr 19, 2002·The Journal of Pharmacology and Experimental Therapeutics·Sylvie A TerlouwDavid S Miller

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