Effects of uremic serum and uremic toxins on hepatic uptake of digoxin

Masayuki Tsujimoto, Yuri Kinoshita, Sumio Hirata, Masaki Otagiri, Hisakazu Ohtani, Yasufumi Sawada

研究成果: Article査読

29 被引用数 (Scopus)

抄録

Not only the renal clearance but also the hepatic clearance of drugs varies with the progression of renal failure. The aim of this study was to investigate the effects of human uremic serum and various uremic toxins on the hepatic uptake of digoxin (DX), a drug mainly excreted into bile in patients with severe renal failure, using isolated rat and human hepatocytes as model systems. Uremic serum inhibited the uptake of DX into rat hepatocytes in a concentration-dependent manner, whereas normal serum did not affect the uptake. In addition, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid, indole-3-acetic acid, indoxyl sulfate, and p-cresol (PC) concentration dependently inhibited the uptake. CMPF and PC at the concentration of 400 μΜ, which is within the plasma concentration range attained in patients with renal failure, inhibited the uptake of DX into rat hepatocytes by 27% and 23%, respectively. In human hepatocytes, 10% uremic serum, 400 μΜ CMPF, and 400 μΜ PC inhibited the uptake of DX by 23.3%, 23.4%, and 28.2%, respectively. In conclusion, our results suggest that hepatic uptake of DX is likely to be inhibited by uremic toxins, such as CMPF and PC, present in the serum of patients with renal failure.

本文言語English
ページ(範囲)576-582
ページ数7
ジャーナルTherapeutic Drug Monitoring
30
5
DOI
出版ステータスPublished - 2008 10
外部発表はい

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

フィンガープリント 「Effects of uremic serum and uremic toxins on hepatic uptake of digoxin」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル