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

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Abstract
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 < 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 < 0.001) and peak serum digoxin concentrations (2.5 ± 0.7 to 3.6 ± 0.8ng/ml; p < 0.001) and in AUC (15.7 ± 1.7 to 23.6 ± 2.9 ng · hr/ml; p < 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. Clinical Pharmacology and Therapeutics (1988) 43, 668–672; doi:10.1038/clpt.1988.93