Effect of pH changes and ethanol on the binding of tricyclic antidepressants to cholestyramine in simulated gastric fluid.

Tricyclic antidepressants have previously been shown by this laboratory to bind significantly (greater than 80%) to cholestyramine in 1.2 mol/L HCl, used to simulate gastric fluid. This finding has important implications for individuals using tricyclic and cholestyramine concurrently, and it may also have potential therapeutic implications in the treatment of tricyclic overdose. In the present study the effects of pH changes and ethanol on this binding were evaluated. Percent binding of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline decreased from 75-90% (pH 1.0) to 35-50% (pH 4.0). Beyond pH 4.0, however, the binding of each antidepressant increased up to 60-75% at pH 6.5. In contrast, ethanol consistently reduced the percent binding of each antidepressant to cholestyramine in 1.2 mol/L HCl until, in the presence of pure ethanol, the binding ranged from 0% (nortriptyline) to only 32% (doxepin). These findings are important since pH varies widely within the gastrointestinal tract and since ethanol may be co-ingested with cholestyramine and antidepressants.