Effects of Uremic Serum Residue on OATP1B1‐ and OATP1B3‐Mediated Pravastatin Uptake in OATP‐Expressing HEK293 Cells and Human Hepatocytes.

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. [ABSTRACT FROM AUTHOR]