title: Effect of fatty acids on the phosphate binding of TRK-390, a novel, highly selective phosphate-binding polymer.
abstract: 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.
authors.affiliation: Pharmacology Laboratory, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kanagawa 248-8555, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nakaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Torii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minakami
authors.forename: Takami
authors.initials: T
authors.lastname: Kanno
authors.forename: Masanori
authors.initials: M
authors.lastname: Murakami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuzuki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Suyama
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Miyamoto
mesh_terms: D000498:Allyl Compounds / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005227:Fatty Acids / Q000494:pharmacology*; D005243:Feces; D006801:Humans; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism* / Q000652:urine; D011073:Polyamines / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D000498:Allyl Compounds; D001647:Bile Acids and Salts; D005227:Fatty Acids; D010710:Phosphates; D011073:Polyamines; D011108:Polymers; C588177:copoly(allylamine-N1,N3-diallylpropane-1,3-diamine)acetate; D019301:Oleic Acid; D013656:Taurocholic Acid
keywords: Hyperphosphatemia; Phosphate absorption; Phosphate binder; Poly (allylamine) polymer