Effect of fatty acids on the phosphate binding of TRK-390, a novel, highly selective phosphate-binding polymer

• Published in: European journal of pharmacology 2013-08, Vol.714 (1-3), p.312-317
• Main Authors: Nakaki, Junko, Yamaguchi, Shinichi, Torii, Yuichi, Inoue, Atsushi, Minakami, Satoshi, Kanno, Takami, Murakami, Masanori, Tsuzuki, Masahiro, Mochizuki, Hidenori, Suyama, Kazuharu, Miyamoto, Mitsuko
• Format: Article
• Language: English
• Subjects: Allyl Compounds - metabolism; Animals; bile acids; Bile Acids and Salts - metabolism; Diet, High-Fat - adverse effects; excretion; fatty acids; Fatty Acids - pharmacology; Feces; hemodialysis; high fat diet; Humans; Hyperphosphatemia; kidney diseases; lipid content; Male; Oleic Acid - pharmacology; patients; pharmacology; Phosphate absorption; Phosphate binder; Phosphates - metabolism; Phosphates - urine; Poly (allylamine) polymer; Polyamines - metabolism; polymers; Polymers - metabolism; Rats; Rats, Sprague-Dawley; Substrate Specificity; Taurocholic Acid - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.07.035

Phosphate binders are used for the treatment of hyperphosphatemia in hemodialysis patients with chronic kidney disease. Sevelamer, a phosphate-binding polymer, has been reported to bind bile acids or fatty acids and thereby decrease its phosphate-binding capacity. The novel phosphate binder TRK-390 is a poly (allylamine) polymer that has been shown to have enhanced phosphate selectivity, with low bile-acid-binding. In this study we evaluated the effect of fatty acids on the phosphate-binding capacity of TRK-390. In the absence of fatty acids and bile acids, the phosphate-binding capacity of TRK-390 was similar to that of sevelamer. In the presence of fatty acids and bile acids, the phosphate-binding capacity of TRK-390 was reduced to 83%; in contrast, that of sevelamer was reduced to 35%. TRK-390 and sevelamer showed a similar effect in lowering urinary phosphate excretion in normal rats fed a normal diet. However, urinary phosphate excretion of rats treated with TRK-390 was reduced by about one half of that obtained with sevelamer, when given with a high-fat diet that had a fat content similar to the diet of hemodialysis patients. TRK-390 was superior in terms of phosphate selectivity in the presence of fatty acids and bile acids in vitro, and the phosphate-binding capacity of TRK-390 in vivo was shown to be less affected by fat in comparison with that of sevelamer. Thus, TRK-390 is expected to be useful as a novel highly selective phosphate binder.