Amlodipine once a day in stable angina: double-blind crossover comparison with placebo

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and short-lived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35-50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine). After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6-12 h postdose. Bioavailability is not affected by the consumption of food. In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism. None of the metabolites of amlodipine has significant calcium antagonist effects in humans. In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node and little or no effect on the resting heart rate. Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose. Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina. Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol and the benzothiazepine calcium antagonist diltiazem. Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates. Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)