Add time:08/16/2019 Source:sciencedirect.com
Cholestyramine resin in a bile acid sequestrant which binds with bile salts in the intestinal lumen to increase the fecal excretion of bile salts and, thus, lower blood serum cholesterol. In order to gain a better understanding of the low in vivo potency of cholestyramine, in vitro equilibrium binding studies, water sorption studies, and resin capacity measurements were performed using cholestyramine and the bile salt sodium glycocholate. Equilibrium binding and water sorption studies entailed equilibrating cholestyramine (1.0–20 mg/mL) with solutions which varied in glycocholate anion concentration (0.20–16.5 mM) and chloride anion concentration (15–150 mM). The resin's practical specific capacity for glycocholate was lower than the practical specific capacity for chloride. This difference suggests that the rigid, bulky bile salt was pore excluded from 10% of the resin's ionogentic sites. A fundamental parameter called the capacity‐corrected molar selectivity coefficient, K Cl‐GC−, was postulated to describe the underlying binding phenomena and was determined by measuring the free glycocholate and chloride anion concentrations; K Cl‐GC− ranged from 9.8 (±0.7) to 18.6 (±0.2) and depended on the square of the free chloride concentration. The capacity‐corrected molar selectivity coefficient was larger than the molar selectivity coefficient due to pore exclusion of glycocholate. A more simple method to calculate the capacity‐corrected molar selectivity coefficient which required less data gave similar values to the more rigorous method (r2 = 0.955).
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