Decreased bioavailability of digoxin due to hypocholesterolemic interventions

Abstract

This study tested the hypothesis that hypocholesterolemic interventions interfere with the bioavailability of orally administered digoxin. Using single dose studies of bioavailability, cumulative six-day urinary digoxin excretion (expressed as a percentage of each individual's control value) was 103% with a normal fiber diet, 82% with a high fiber diet, 83% with 4 g of cholestyramine, 69% with 8 g of cholestyramine, 80% with 8 g cholestyramine administered eight hours before digoxin, 92% with 8 g of cholestyramine administered eight hours after dogixin and 80% after completion of two weeks of treatment with para-aminosalicylic acid. Analysis of the urinary excretion data and associated serum levels revealed significant interference with the absorption of digoxin in all instances except for administration of digoxin either with a normal fiber diet or administration eight hours before cholestyramine. The cholestyramine-digoxin interaction was further studied using steady-state investigation of bioavailability. Serum levels and daily urinary digoxin excretions (expressed as a percentage of each individual's control value) were: 75% and 80% for digoxin administered simultaneously with 4 g of cholestyramine daily; 69% and 86% for digoxin administered simultaneously with the first daily dose of cholestyramine given as 4 g, four times a day, and 96% and 93% with cholestyramine 8 g twice a day, eight hours before and eight hours after digoxin ingestion. Serum levels and urinary excretions for all three cholestyramine interventions were significantly less than control. The results of the single dose and steady-state experiments demonstrate that cholestyramine's reduction of digoxin oral bioavailability is related to the dose of cholestyramine and the proximity of the time of administration of the two drugs.