Update on the Pharmacokinetics and Redox Properties of Protein-Bound Uremic Toxins

• Published in: Journal of pharmaceutical sciences Vol. 100; no. 9; pp. 3682 - 3695
• Main Authors: Watanabe, Hiroshi, Miyamoto, Yohei, Otagiri, Masaki, Maruyama, Toru
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2011; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: albumin; Animals; antioxidants; Biological and medical sciences; free radicals; General pharmacology; Humans; Medical sciences; membrane transport; metabolic clearance; organic anion transporters; Oxidation-Reduction; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; protein binding; renal transport; Toxins, Biological - metabolism; Uremia - metabolism; renal transport; free radicals; antioxidants; albumin; organic anion transporters; metabolic clearance; pharmacokinetics; membrane transport; protein binding; Kidney disease; Urinary system disease; Pharmaceutical technology; Albumin; Updating; Clearance; Antioxidant; Metabolism; Free radical; Kidney; Binding protein; Toxin; Membrane transport; Renal failure; Organic anion transporter; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22592

Protein-bound uremic toxins, such as indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, p-cresyl sulfate, hippuric acid, and indoleacetic acid, have been the subjects of extensive investigations. In this review, we summarized the recent works providing the new insight on the pharmacokinetics and redox properties of these uremic toxins. They have a common characteristic of being difficult to remove by conventional dialysis because they all bind tightly to serum albumin. They are transported via organic anion transporters to various tissues, and accumulate not only in the kidney but also in other tissues including vascular endothelial cells, smooth muscle cells, osteoblasts, and the central nervous system. Accumulated uremic toxins alter nonrenal drug clearance. Intracellular accumulated uremic toxins have been linked to the induction of oxidative stress and the stimulation of proinflammatory cytokines through the production of reactive oxygen species, which play a role in the progression of chronic kidney disease and the development of complications. Unfortunately, despite the massive amount of information on the undesirable effects of uremic toxins, methods for improving the detoxification of these toxins appear to be lacking. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3682–3695, 2011