Chronic cyclosporine administration induces renal P-glycoprotein in rats.
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.
Liu
J
J
Pharmaceutics Division, PHR 4.214E, College of Pharmacy, The University of Texas at Austin, 78712-1074, USA.
Brunner
L J
LJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007279:Injections, Subcutaneous; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine