Combined Effects of Benidipine and Diltiazem on Cardiohemodynamics in Anesthetized Dogs

Abstract

We examined the combined effects of the calcium channel blockers 1,4-dihydropyridine (benidipine) and benzothiazepine (diltiazem) on cardiohemodynamics in anesthetized dogs. Benidipine (3 m mg/kg) lowered blood pressure (BP) slightly and continuously increased coronary flow (CF). Diltiazem (300, 1000 m mg/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 m mg/kg) and diltiazem (300 m mg/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.

Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

“…Combination effects of benidipine and diltiazem for the treatment of angina have also been reported in rats (90). Benidipine shows more vascular selectivity and less negative inotropic activity compared to diltiazem, and induces a longer-lasting increase in coronary blood flow (96,97). Diltiazem also increases coronary blood flow, but this effect is transient, unlike the similar effect of benidipine (97).…”

“…Benidipine shows more vascular selectivity and less negative inotropic activity compared to diltiazem, and induces a longer-lasting increase in coronary blood flow (96,97). Diltiazem also increases coronary blood flow, but this effect is transient, unlike the similar effect of benidipine (97). Diltiazem has a beneficial effect in reducing myocardial oxygen consumption by reducing heart rate, and this effect contributes to its antianginal effects.…”