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

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. © 2013 Elsevier B.V. All rights reserved.

Citation

Junko Nakaki, Shinichi Yamaguchi, Yuichi Torii, Atsushi Inoue, Satoshi Minakami, Takami Kanno, Masanori Murakami, Masahiro Tsuzuki, Hidenori Mochizuki, Kazuharu Suyama, Mitsuko Miyamoto. Effect of fatty acids on the phosphate binding of TRK-390, a novel, highly selective phosphate-binding polymer. European journal of pharmacology. 2013 Aug 15;714(1-3):312-7

PMID: 23911881

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