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Effects of Uremic Serum Residue on OATP1B1‐ and OATP1B3‐Mediated Pravastatin Uptake in OATP‐Expressing HEK293 Cells and Human Hepatocytes
Author(s) -
Uchiyama Hitoshi,
Tsujimoto Masayuki,
Kimura Akari,
Yuki Eriko,
Saiki Takashi,
Yoshida Takuya,
Furukubo Taku,
Izumi Satoshi,
Yamakawa Tomoyuki,
Tachiki Hidehisa,
Minegaki Tetsuya,
Nishiguchi Kohshi
Publication year - 2019
Publication title -
therapeutic apheresis and dialysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 53
eISSN - 1744-9987
pISSN - 1744-9979
DOI - 10.1111/1744-9987.12758
Subject(s) - medicine , pravastatin , hek 293 cells , pharmacology , receptor , cholesterol
Patients with end‐stage renal disease have increased plasma concentrations of statins, which is a risk factor for rhabdomyolysis, as well as elevated levels of uremic toxins (UTs). We investigated the effects of uremic serum residue and UTs on organic anion‐transporting peptide (OATP1B1)‐ and OATP1B3‐mediated pravastatin uptake. We evaluated the effects of normal serum residue with four UTs (hippuric acid, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furan propionate, indole‐3‐acetic acid, and 3‐indoxyl sulfate) and uremic serum residue on pravastatin uptake by OATP1B1‐ or OATP1B3‐expressing HEK293 cells. Furthermore, we assessed the contribution of each transporter using cryopreserved human hepatocytes. Uremic serum residue and UTs significantly inhibited OATP1B1‐mediated pravastatin uptake. Uremic serum residue accelerated OATP1B3‐mediated pravastatin uptake, while UTs had no effect. There was no difference in pravastatin uptake between uremic‐ and normal serum residue‐treated hepatocytes. The results suggest that the effects of uremic serum on pravastatin hepatic uptake may be considered negligible in end‐stage renal disease patients.