Sevelamer (hydrochloride) 

Sevelamer hydrochloride is an orally active polymeric phosphate binder and bile acid sequestrant. Sevelamer hydrochloride binds dietary phosphate in the gastrointestinal tract, reducing phosphate absorption and serum phosphorus levels, and reduces urinary phosphate excretion. Sevelamer hydrochloride binds polyanion bile acids, increases bile acid faecal excretion, and reduces total cholesterol and LDL cholesterol levels. Sevelamer hydrochloride can be used for the research of hyperphosphataemia, hyperparathyroidism, chronic renal failure, kidney disease, and type 2 diabetes^{[1][2][3][4][5][6][7][8]}.

Sevelamer hydrochloride exhibits pH-dependent, reversible binding of AGE-BSA, with >80% binding at intestinal pH (7.0) and less than 5% binding at stomach pH (1.0), while showing minimal binding to unmodified BSA^[6].
Sevelamer (15 mg/mL; pH=6 or 8) hydrochloride decreases serum levels of gut-derived uremic toxins (such as IAA) or limits the elevation of gut-derived uremic toxins (initial concentration=1 μg/mL or 10 μg/mL)^[7].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Sevelamer hydrochloride produces a dose-dependent reduction in urinary phosphate excretion of up to 96% in rats with normal renal function, with greater faecal phosphate excretion than calcium carbonate^[1].
Sevelamer hydrochloride improves renal function in a rat model of long-term uraemia by reducing renal calcification^[1].
Sevelamer (1% mixed in diet; p.o.; 2-3 weeks) hydrochloride does not alter serum phosphate levels in uremic WT mice, but further decreased serum phosphate levels in uremic Npt2b / mice in uremic mouse model^[8].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

186.08 (monomer)

(C₃H₇N.C₃H₅ClO)x.xHCl

152751-57-0

Solid

White to off-white

NCC(CC(CC)CNCC(O)CNCC(C)CC(CC)CN)CC.[m].Cl.[m].[c].[b].[a]

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Henderson J, et al. Sevelamer. Nephron Clin Pract. 2003;94(3):c53-c58.

  [2]. Chertow GM, et al. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62(1):245-252.

  [3]. Tonelli M, et al. Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients. Nephrol Dial Transplant. 2007;22(10):2856-2866.

  [4]. Block GA, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int. 2005 Oct;68(4):1815-24.

  [5]. Chue CD, et al. Cardiovascular effects of sevelamer in stage 3 CKD. J Am Soc Nephrol. 2013;24(5):842-852.

  [6]. Vlassara H, et al. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol. 2012;7(6):934-942.

  [7]. Bennis Y, et al. The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Toxins (Basel). 2019 May 17;11(5):279.  [Content Brief]

  [8]. Susan C Schiavi, et al. Npt2b deletion attenuates hyperphosphatemia associated with CKD. J Am Soc Nephrol. 2012 Oct;23(10):1691-700.  [Content Brief]