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 less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 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.
Hedman
A
A
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Angelin
B
B
Arvidsson
A
A
Beck
O
O
Dahlqvist
R
R
Nilsson
B
B
Olsson
M
M
Schenck-Gustafsson
K
K
D001646:Bile / Q000737:chemistry; D001659:Biliary Tract / Q000378:metabolism*; D004077:Digoxin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D014700:Verapamil / Q000097:blood / Q000494:pharmacology*
D004077:Digoxin; D014700:Verapamil