Digoxin-verapamil interaction: In vitro studies in rat tissue

Recent studies have shown a significant increase in plasma digoxin concentration during verapamil treatment. This phenomenon has been attributed in part to reduced renal clearance of digoxin owing to inhibition of the digoxin tubular secretory process. We studied the influence of digoxin-verapamil interaction on [¹²⁵I]digoxin uptake by various rat tissues in vitro, employing the tissue slice technique. Slice/medium digoxin ratios (mean ± SD) were: Kidney, 4.09 ±0.60; heart, 3.63 ± 0.41; liver, 3.93 ± 0.39; and muscle, 3.55 ± 0.55. Addition of verapamil to the incubation medium resulted in a 15.6% reduction of digoxin uptake by kidney tissue, to 3.38 ± 0.49 (p < 0.0005). Verapamil failed to reduce digoxin uptake in liver, heart, or striated muscle. We conclude that the renal cortical transport mechanism of digoxin may be inhibited by verapamil. In contrast, the unaffected uptake of digoxin in heart or muscle indicates that the increase in serum digoxin concentration in the presence of verapamil is not caused or accompanied by redistribution of digoxin from the heart or striated muscle.