Transport of statins by multidrug resistance-associated proteins 1 and 5.

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Tác giả: Feng Deng, Mikko Neuvonen, Mikko Niemi, Suvi-Kukka Tuomi

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 714048

Statins are widely used in the treatment of hypercholesterolemia but also associated with muscle-related adverse effects. Multidrug resistance-associated protein (MRP) 1 and 5 are expressed in the skeletal muscle, where they may regulate intramuscular levels of their substrates. Here, we investigated the transport of various statins by MRP1 and MRP5 with the vesicular transport assay. Statin concentrations in the vesicles were determined with liquid chromatography tandem mass spectrometry. At 6 µM statin concentration, MRP1 transported both 3R,5S-fluvastatin and 3S,5R-fluvastatin with uptake ratios of 2.6 and 2.0. MRP5 transported 3R,5S-fluvastatin, 3S,5R-fluvastatin, and 10 µM pitavastatin with uptake ratios of 2.9, 3.7, and 2.6, respectively. Atorvastatin was only a weak substrate of MRP5 with an uptake ratio of 1.6 and was therefore not investigated further. In concentration-dependent transport experiments, racemic fluvastatin was transported by MRP1 and MRP5 with apparent affinities (K
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