Biol. Pharm. Bull. 29(4) 730—734 (2006)

treatment of cardiovascular disorders, such as angina pectoris and hypertension. The therapeutic effectiveness of the blockers in these disease states is based on a range of hemodynamic actions, including effects on blood vessels, hearts, and kidneys. Calcium channel blockers are classified into the following three groups on the basis of chemical structures, which show different pharmacological and therapeutic properties: (a) 1,4-dihydropyridines (DHPs), (b) benzothiazepines and (c) phenylalkylamines. DHPs exhibit higher selectivity for vasculature than benzothiazepine (diltiazem) and have less effects on nodal tissue of the heart. Among the DHPs, benidipine has a high selectivity for vasculature. When the vascular selectivity of various calcium antagonists was evaluated using isolated coronary arteries and right ventricular papillary muscles of dogs, the coronary artery selectivity of benidipine was 14 times higher than that of nifedipine and 19 times higher than that of amlodipine. In the treatment of angina pectoris, monotherapy using antianginal drugs is generally not completely effective for all types of angina pectoris. Combination therapy employing different types of agents has been used in an effort to improve the clinical benefits of monotherapy. We reported recently that the combination of diltiazem and benidipine exerted potent antianginal effects in the vasopressin-induced angina rat model. However, there have been no published reports concerning the hemodynamic profile of the combination of diltiazem and benidipine. Therefore, in the present study we examined the hemodynamic effects of diltiazem, benidipine, and the combination of these drugs in anesthetized dogs. In addition, we evaluated the plasma level of the drugs. MATERIALS AND METHODS