Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats.

Abstract

The purpose of the present study was to examine the pharmacokinetic properties of indoxyl sulphate, a harmful uraemic toxin that accumulates during chronic renal failure. The pharmacokinetics and tissue distribution of indoxyl sulphate were examined in normal and 5/6 nephrectomized (CRF) rats. The uptake process of indoxyl sulphate by rat renal cortical slices in vitro was also investigated. Endogenous indoxyl sulphate was found to be mainly distributed in the kidney. The rate of elimination of indoxyl sulphate from plasma was lower in CRF rats compared with sham-operated rats. The majority of intact indoxyl sulphate was excreted in the urine. In renal cortical slice experiments, uptake of indoxyl sulphate was a saturable process with a K(m) of 43.0 microm. Furthermore, sulphate conjugates, such as oestrone sulphate and dehydroepiandrosterone sulphate, inhibited the uptake of indoxyl sulphate to a greater extent than PAH. Thus, indoxyl sulphate is primarily eliminated from the plasma via the kidney by active tubular secretion, and renal uptake of indoxyl sulphate appears to be mediated by an organic anion transport system with a high affinity for oestrone sulphate and dehydroepiandrosterone sulphate.

• Authors: Tsuneo Deguchi, Mikio Nakamura, Yasuhiro Tsutsumi, Ayaka Suenaga, Masaki Otagiri
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 24 Issue 8 Pg. 345-55 (Nov 2003) ISSN: 0142-2782 [Print] England
• PMID: 14595703 (Publication Type: Journal Article)
• Copyright: Copyright 2003 John Wiley & Sons, Ltd.

Chemical References

• Indican

Topics

• Animals
• Chromatography, High Pressure Liquid
• Disease Models, Animal
• Dose-Response Relationship, Drug
• In Vitro Techniques
• Indican (blood, metabolism, pharmacokinetics, urine)
• Infusions, Intravenous
• Kidney (metabolism)
• Kidney Failure, Chronic (metabolism)
• Male
• Nephrectomy
• Rats
• Rats, Wistar
• Tissue Distribution