Chronic Verapamil Administration Research Articles

Influence of verapamil therapy on left ventricular performance at rest and during exercise in hypertrophic cardiomyopathy

To determine the hemodynamic effect of verapamil at rest and during exercise, 18 patients with hypertrophic cardiomyopathy were studied before and after 7 weeks of treatment with oral verapamil (maximal dose, 720 mg/day). At rest and at peak exercise, verapamil produced a significant increase in left ventricular (LV) systolic performance in terms of stroke volume index (rest, from 43 ± 11 to 53 ± 11 ml/m 2, p < 0.001; exercise, from 46 ± 11 to 51 ± 10 ml/m 2, p < 0.01), whereas heart rate decreased (rest, from 81 ± 14 to 70 ± 11 min −1, p < 0.001; exercise, from 150 ± 21 to 141 ± 18 min −1, p < 0.01). Cardiac index at rest and during exercise remained unchanged. Systolic vascular resistance did not change at rest, but decreased significantly during exercise (974 ± 243 to 874 ± 174 dynes s cm −5; p < 0.05). After verapamil administration, pulmonary artery pressures did not change at rest, but decreased significantly during exercise. This was probably due to a shift in the LV pressure-volume relation. The improvement in LV hemodynamics was associated with a significant increase in exercise capacity. The findings of this study indicate that in patients with hypertrophic cardiomyopathy, hemodynamic improvement at rest and during exercise can be achieved by chronic administration of verapamil.

Prolongation of verapamil elimination kinetics during chronic oral administration

The elimination of verapamil and its n-demethylated metabolite, norverapamil, was studied in nine patients with chronic atrial fibrillation after the first oral verapamil dose and during chronic oral verapamil administration. Significant increases ( p < 0.01) were seen in the elimination half-lives ( t 1 2 's ) of both verapamil ( 6.4 ± 3.5 to 12 ± 5 hours, x ± SD ) and norverapamil (10.3 ± 6 to 16.5 ± 7 hours) during chronic oral verapamil administration. These pharmacokinetic observations have important clinical implications for the rational long-term administration of this agent. Once steady-state serum concentrations have been achieved during chronic verapamil administration, verapamil doses should be given at less frequent intervals or in smaller doses in order to produce the desired serum concentration and therapeutic response and to minimize unwanted or toxic drug effects.

Prolongation of verapamil elimination kinetics during chronic oral administration

The elimination of verapamil and its n-demethylated metabolite, norverapamil, was studied in nine patients with chronic atrial fibrillation after the first oral verapamil dose and during chronic oral verapamil administration. Significant increases (p less than 0.01) were seen in the elimination half-lives (t 1/2's) of both verapamil (6.4 +/- 3.5 to 12 +/- 5 hours, mean +/- SD) and norverapamil (10.3 +/- 6 to 16.5 +/- 7 hours) during chronic oral verapamil administration. These pharmacokinetic observations have important clinical implications for the rational long-term administration of this agent. Once steady-state serum concentrations have been achieved during chronic verapamil administration, verapamil doses should be given at less frequent intervals or in smaller doses in order to produce the desired serum concentration and therapeutic response and to minimize unwanted or toxic drug effects.