Binding of Bile Acids to Anion-exchanging Drugs in Vitro

Abstract

Equal amounts of anion exchanger of the drugs, Secholex, Colestipol, Cuemid, and Questran, were incubated at 37 °C with human duodenal fluid containing about 7 mM total bile acid. Binding of bile acid to Questran, which contains about 45% cholestyramine, was fastest: concentration of unbound bile acid after 2 hours was less than 3 mM compared to about 5 mM in the solutions incubated with the other drugs, including Cuemid, which contains about 83% cholestyramine. After 24 hours, differences were less marked, but binding to Questran was still greatest. Glycocholic acid was least efficiently bound, especially to Secholex and Cuemid, The differences in rates of binding were unaffected by preincubation of the drugs with 1N HCl to simulate stomach conditions. Although differences between the cholestyramine components of Cuemid and Questran are not ruled out, it is possible that one or more of the other components of Questran significantly affect the in vitro binding of bile acids. Cholestyramine in the form of Questran may be the drug of choice in the treatment of hypercholesterolemia, in which reduction of the bile acid pool is desirable. In cholegenic diarrhoea, however, one of the drugs with lower affinity for glycocholic acid may be preferable.

Key-words:

• Bile acids and salts
• biopharmaceutics
• cholestyramine
• drug compounding
• hypercholesteremia
• hyperlipemia
• ion exchange resins