Effect of Dihydropyridine Calcium Channel Blockers on the Plasma Digoxin Level

The effects of four dihydropyridine calcium channel blockers (nifedipine, nisoldipine, nitrendipine and manidipine) on the plasma digoxin level were studied in patients and the effects of nitrendipine and nisoldipine were compared in beagle dogs . In the clinical study, the mean plasma concentration of digoxin was significantly higher during combined administration with nitrendipine than with the other calcium channel blockers. In addition, the digoxin level was decreased by about 50% at one month after changing the calcium channel blocker from nitrendipine to nisoldipine. In dogs, combined administration with nitrendipine resulted in a significantly higher plasma digoxin level after 2 and 4 hrs and a significantly larger mean area under the plasma concentration time curvecompared with administration without nitrendipine (p<0.05). These findings demonstrate that the plasma concentration of digoxin is influenced by dihydropyridine calcium channel blockers, with nitrendipine increasing the digoxin level more than the other agents tested. Since digoxin has a narrow therapeutic range, careful monitoring of the plasma digoxin level during combined therapy with nitrendipine is suggested to minimize the risk of toxicity.