1 In a placebo controlled double-blind study including 10 patients with heart failure the nisoldipine/digoxin interaction was studied. 2 Nisoldipine was shown to elevate digoxin plasma concentrations significantly by about 15% (trough levels). 3 During chronic combination therapy with nisoldipine trough levels and plasma concentrations 4 h after the morning dose of digoxin were 1.35 ± 0.14 and 1.92 ± 0.16 ng ml-' respectively, whereas they averaged to 1.16 ± 0.14 and 1.52 + 0.16 ng ml-1 with digoxin and placebo (P < 0.05; mean + s.e. mean). 4 Systolic time intervals were significantly altered by nisoldipine co-administration compared with digoxin plus placebo. 5 In certain patients the elevation of digoxin plasma levels due to nisoldipine coadministration could be of clinical relevance.

No abstract

Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its alpha-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.