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Preclinical studies of VS?505: a non?absorbable highly effective phosphate binder #MMPMID27156057
Wu?Wong JR; Chen Y; Wong JT; Wessale JL
Br J Pharmacol 2016[Jul]; 173 (14): 2278-89 PMID27156057show ga
Background and Purpose: Phosphate imbalance is often present in chronic kidney disease (CKD), and it contributes to a higher cardiovascular mortality rate. A phosphate binder is typically part of a treatment strategy for controlling phosphate imbalance. However, safety concerns and low compliance are two well?recognized disadvantages of on?market phosphate binders. This report describes the preclinical studies of VS?505, a non?absorbable, calcium? and aluminum?free, plant?derived polymer currently being evaluated in haemodialysis patients in Australia. Experimental Approach: Normal Sprague Dawley (SD) rats or uraemic SD rats induced by 5/6 nephrectomy fed a high?phosphate diet were treated with VS?505 or sevelamer (0.05?10% in food) for 5 and 28 days respectively. Key Results: Urinary and serum phosphate levels were significantly elevated in untreated rats, and were decreased by VS?505 and sevelamer. VS?505 increased faecal phosphate levels in a dose?dependent manner. High?phosphate diet also caused an increase in serum FGF?23 and parathyroid hormone in nephrectomized (NX) rats, effects prevented by VS?505 or sevelamer. Significant aortic calcification was observed in NX rats treated with 5% sevelamer, whereas VS?505 at all doses tested did not show effects. VS?505 had no effects on small intestine histomorphology and intestinal sodium?dependent phosphate cotransporter gene expression. In vitro characterizations showed that VS?505 has a relatively high density and low expansion volume when exposed to simulated gastric fluid. Conclusions and Implications: VS?505 is a safe and effective phosphate binder and may offer the advantage of having a reduced pill burden and minimal GI side effects for CKD patients.
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Br+J+Pharmacol 2016 ; 173 (14): 2278-89
