Combined Effects of Benidipine and Diltiazem on Cardiohemodynamics in Anesthetized Dogs

We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on cardiohemodynamics in anesthetized dogs. Benidipine (3 μg/kg) lowered blood pressure (BP) slightly and continuously increased coronary flow (CF). Diltiazem (300, 1000 μg/kg) decreased BP, heart rate (HR), and the maximum rate of rise of left ventricular pressure (LV dP/dt max) with the increase of doses. Diltiazem increased CF, though it was transient when compared to benidipine. A combination of benidipine (3 μg/kg) and diltiazem (300 μg/kg) showed continuous decreases in BP, HR, and LV dP/dt max, and an increase in CF that was similar to that recorded for the benidipine group. The level of double product (DP: systolic BP×HR, an index of myocardium energy consumption) in the combination group was significantly lower than that of the benidipine group. The plasma concentrations of benidipine and diltiazem in the combination group were similar to those of the groups receiving either drug. These results demonstrate that the combination of benidipine and diltiazem increases CF more continuously than diltiazem alone, and decreases DP more potently than benidipine alone, indicating that the combination therapy possesses favorable properties as a treatment for angina pectoris. Therefore, the combination of benidipine and diltiazem is suggested as a useful treatment for improving the clinical benefits of monotherapy for angina, compared with the use of diltiazem alone at higher doses.