Interaction of warfarin and nonsystemic gastrointestinal drugs

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Abstract
The absorption and pharmacologic action of warfarin may be influenced by such factors as gut motility, pH, solubility, and chemical binding. To investigate the possible interaction of warfarin with nonsystemic gastrointestinal drugs in clinical use, (1) cholestyramine, (2) an antacid mixture containing magnesium and aluminum hydroxide, and (3) psyllium hydrophyllic mucilloid were studied in 6 normal subjects. In a series of experiments average therapeutic doses of each drug were administered concurrently with a single oral dose of warfarin 40 mg. Cholestyramine was found to decrease significantly mean plasma warfarin levels and the hypoprothrombinemic effect of warfarin even after a 3 hour interval between ingestion of the two drugs. Neither the antacid nor psyllium colloid was found to alter plasma concentrations or pharmacologic action of warfarin. In vitro experiments demonstrated significant binding of warfarin to cholestyramine at a pH above its pKa of 5.5.

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