01 January 2008
In vitro investigation of MRP 2 in the cyclosporine A – pravastatin interplay
R.l Kato, M. Nishide, C. Kodzu, Y. Ijiri, K. TanakaAnn Transplant 2008; 13(1): 34-34 :: ID: 880190
Abstract
Background: Cyclosporine A (CsA) has been used to treat a variety of autoimmune diseases. It is reported that CsA is metabolized by CYP3A and excreted via P-glycoprotein and multidrug resistant protein (MRP) 2 in humans. Pravastatin has been used to treat hyperlipidemia, and it is reported that pravastatin is excreted via MRP2 in humans. We had two cases where the blood CsA level was increased following pravastatin administration. It is suggested that CsA interacted with pravastatin via MRP2. In this study, we investigated the effects of pravastatin on CsA transport via MRP2.
Material/Methods: Caco 2 cells were seeded on Transwell® at a density of 105 cells/well. Calcein, a substrate of MRP, was put into Caco 2 cells, and CsA (5, 50 μM) and pravastatin (0.1, 1.0 mM) were added to the apical and basolateral sides (n = 6). After a 30 min incubation, calcein was effl uxed from Caco 2 cells, and the calcein level of the culture medium was assayed. CsA was put into Caco 2 cells, and pravastatin (0.1, 1.0 mM) was added to the apical and basolateral sides (n=3). After 1 hour of incubation, CsA was effluxed from Caco 2 cells and the CsA level of the culture medium was assayed.
Results: The calcein effl ux to the apical side was decreased significantly by the addition of pravastatin (1.0 mM) and CsA (5, 50 μM), respectively. The CsA efflux to the apical side was decreased significantly by the addition of pravastatin (1.0 mM).
Conclusions: The results demonstrate that CsA transport may
be inhibited competitively by pravastatin via MRP2.
Keywords: Cyclosporine, hyperlipidemia, Medullary Thyroid Cancer
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