Study of Pharmacokinetic and Pharmacodynamic Interaction between Nitrendipine and Digoxin

Abstract

Nitrendipine is a new dihydropyridine-type calcium antagonist. We studied the effect of 20 mg b.i.d., orally, on steady-state digoxin concentrations, renal excretion, and hemodynamic parameters in 10 healthy male volunteers. A loading dose of 0.6 mg β-acetyldigoxin was given on days 1, 2, and 3. β-acetyldigoxin, 0.3 mg once daily, was given from day 4 to day 29 of the study. Nitrendipine coadministration lasted from day 9 until day 22. Equilibrium was assumed for days 6–8 (monotherapy), 20–22 (coadministration), and 27–29 (monotherapy after nifedipine withdrawal). Means and 95% confidence intervals of the treatment periods were compared. Digoxin concentrations slightly decreased from 0.7 ± 0.15 to 0.64 ± 0.14 and 0.59 ± 0.1 (mean ± SD). Urinary excretion during 24 h was fairly constant and did not show a remarkable effect of nitrendipine coadministration or withdrawal. The amounts excreted were 197.8 ± 19.1 (monotherapy), 193.2 ± 30.2 (coadministration), and 182.5 ± 31.8 μg/24 h. Renal digoxin clearance was 2.7 ± 0.4 and 2.9, ± 0.4 ml/min/kg on monotherapy and 2.9 ± 0.4 ml/min/kg on coadministration. Hemodynamic changes were small and not clinically relevant. They did not reflect an effect of nitrendipine.