Digoxin-verapamil interaction: Reduction of biliary but not renal digoxin clearance in humans

The interaction between digoxin and verapamil was studied in six patients (mean age ± SD, 61 ± 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 ± 0.24 to 1.15 ± 0.40 nmol/L (p < 0.01). The biliary clearance of digoxin decreased by 43%, from 187 ± 89 to 101 ± 55 ml/min (p < 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 ±31 versus 173 ± 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route. Clinical Pharmacology and Therapeutics (1991) 49, 256–262; doi:10.1038/clpt.1991.26