Abstract
The effects of the hypocholesterolemic agent cholestyramine, a nonabsorbable anion-exchange resin, on the rate and extent of absorption of dicumarol and tromexan were assessed in rats by following the time course of either coumarin anticoagulant in the plasma. Concurrent oral administration of a single 250 mg/kg dose of the resin and a 100 mg/kg dose of either anticoagulant resulted in significant reductions in control plasma anticoagulant levels at all experimental times; control peak plasma levels of dicumarol and tromexan were reduced by 66 and 80%, respectively. The markedly lower, pre-peak plasma levels of either anticoagulant in resin-treated animals, coupled with the results of in vitro binding studies, indicate that cholestyramine is capable of rapidly and strongly interacting with both drugs in the gastrointestinal tract, thereby decreasing their rates of absorption. Based on area under the plasma concentration vs. time curve measurements, it was established that only 55% of the oral dose of dicumarol and 28.8% of the oral dose of tromexan were absorbed in the presence of the resin as compared to that absorbed in control animals. The rate, but not the extent, of dicumanol absorption was also significantly reduced when cholestyramine was orally administered 3 hours prior to dicumarol administration. The results of this investigation suggest that an undesirable drug interaction could occur in patients receiving cholestyramine and either dicumarol or tromexan, simultaneously.
Footnotes
- Received April 29, 1974.
- Accepted June 14, 1974.
- © 1974 by The Williams & Wilkins Company