Toxic digoxin-drug interactions: the major role of renal P-glycoprotein

The clinical use of digoxin is complicated by a large number of drug interactions leading to severe toxicity of the cardiac glycoside. The discovery that digoxin is actively secreted by the renal tubular cell via the p-glycoprotein drug efflux pump has led us to examine whether commonly interacting drugs do so by inhibiting renal tubular secretion of digoxin. We review digoxin-drug interactions which have been studied kinetically in humans, where there are sufficient data on renal clearance of digoxin and GFR.