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Equilibrium and kinetic factors influencing bile sequestrant efficacy
1College of Pharmacy, University of Michigan, Ann Arbor 48109.
Pharmaceutical Research
|May 1, 1992
Summary
Chloride ions significantly reduce cholestyramine
Area of Science:
- Gastroenterology
- Pharmacology
- Biochemistry
Background:
- Cholestyramine is a bile sequestrant used to treat hypercholesterolemia.
- Its efficacy in vivo is not fully understood, prompting further investigation into binding mechanisms.
Purpose of the Study:
- To investigate in vitro bile salt binding equilibria and kinetics of cholestyramine.
- To determine factors influencing cholestyramine's in vivo efficacy as a bile sequestrant.
Main Methods:
- In vitro equilibrium and kinetic binding studies of cholestyramine with glycocholate (GCH).
- Measurement of chloride ion displacement using a chloride selective electrode.
- Comparison of in vitro findings with human clinical data.
Main Results:
- Physiologic chloride concentrations reduced glycocholate binding by over twofold and displaced bound glycocholate.
- Bile salt binding to cholestyramine occurs via ion exchange.
- Anion binding competition alone does not explain cholestyramine's limited efficacy.
Conclusions:
- Cholestyramine exhibits adequate binding potential, with interferences not being major factors.
- Rapid binding and displacement kinetics suggest quick equilibration in the GI tract.
- Low cholestyramine efficacy is primarily attributed to poor prevention of ileal bile salt reabsorption.