Comparative effects of verapamil and isradipine on steady-state digoxin kinetics

The effects on the steady-state digoxin pharmacokinetics of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), were compared. Nineteen healthy white men, aged 23 to 40 years, ingested 0.25 mg digoxin tablets every 12 hours for two consecutive periods of 2 weeks. Each subject also received one of the calcium channel blockers during one of these periods, with agent and sequence randomized. Analyst-blind RIA serum digoxin determinations demonstrated that the nine subjects who received isradipine, 5 mg t.i.d., had a small increment in peak digoxin level from 2.3 +/- 0.6 to 2.9 +/- 0.7 ng/ml (p less than 0.05) but no significant change in steady-state level or AUC over 12 hours. By contrast, the 10 subjects who received verapamil, 80 mg t.i.d., showed significant increases in steady-state (0.9 +/- 0.1 to 1.3 +/- 0.2 ng/ml; p less than 0.001) and peak serum digoxin concentrations (2.5 +/- 0.7 to 3.6 +/- 0.8 ng/ml; p less than 0.001) and in AUC (15.7 +/- 1.7 to 23.6 +/- 2.9 ng . hr/ml; p less than 0.001). Neither calcium channel blocker reduced renal digoxin clearance. Verapamil increases digoxin levels without affecting renal clearance. Isradipine has no clinically important interaction with digoxin.