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Bile acid binding to sevelamer HCl.
William Braunlin1, Eugene Zhorov, Amy Guo
1GelTex Pharmaceuticals, Waltham, Massachusetts, USA. william.braunlin@verizon.net
Kidney International
|July 12, 2002
Summary
Sevelamer effectively lowers serum phosphate and LDL cholesterol in dialysis patients. Its strong binding to bile acids, enhanced by oleic acid, explains its cholesterol-lowering effects.
Area of Science:
- Biochemistry
- Pharmacology
- Nephrology
Background:
- Sevelamer hydrochloride (Renagel) is clinically proven to reduce serum phosphate in hemodialysis patients.
- Treatment with sevelamer consistently shows a significant reduction in low-density lipoprotein (LDL) cholesterol.
Purpose of the Study:
- To investigate the binding characteristics of sevelamer with bile acids and oleic acid.
- To elucidate the mechanism behind sevelamer's LDL cholesterol-lowering effect.
Main Methods:
- Equilibrium binding assays using sevelamer incubated with bile acids and oleic acid.
- Quantification of free ligand concentrations via high-pressure liquid chromatography (HPLC).
- Flow kinetics determined using a cylindrical flow cell mimicking in vivo conditions.
Main Results:
- Sevelamer exhibits cooperative and high-capacity binding of bile acids.
- Oleic acid enhances bile acid binding and significantly reduces their release rate.
- Even at saturating oleic acid concentrations, sevelamer retains substantial bile acid binding capacity.
Conclusions:
- Sevelamer's robust bile acid binding properties offer a clear explanation for its efficacy in lowering LDL cholesterol.
- These binding characteristics are relevant for both hemodialysis patients and healthy individuals.