Effect of Dihidropyridine Calcium Antagonists on the Plasma Digoxin Level. II : Involvement of Renal Function

The effects of four dihydropyridine calcium antagonists (manidipine, benidipine, amlodipine and nitrendipine) on the plasma digoxin level and the renal hemodynamics were studied in both patients and conscious normotensive beagle dogs.In the clinical study, the combined administration of digoxin with calcium antagonists elevated, plasma digoxin levels compared with digoxin monotherapy, however, the difference was not significant. In dogs, the combined administration of digoxin with benidipine or nitrendipine resulted in a significantly higher plasma digoxin level after 8 and 24 hrs, respectively, but it did not affect the mean area under the plasma digoxin concentration time curve.In a renal hemodynamic study in dogs, the glomerular filtration rate was observed to decrease significantly following the combined administration with manidipine. Furthermore, the filtration fraction decreased significantly after the administration of manidipine and benidipine, but it did not affect the renal plasma flow. In addition, amlodipine slightly decreased the glomerular filtration rate. On the other hand, nitrendipine did not alter the renal hemodynamics.Since dihydropyridine calcium antagonists demonstrate different effects on renal hemodynamics during the combined administration of digoxin, administering the appropriate dosage of digoxin during combined therapy with calcium antagonists is therefore necessary to minimize the risk of digoxin toxicity.