Pharmacokinetics and additional anti-ischaemic effectiveness of amlodipine, a once-daily calcium antagonist, during acute and long-term therapy of stable angina pectoris in patients pre-treated with a beta-blocker

Amlodipine 10 mg was evaluated for additional anti-ischaemic and anti-anginal efficacy in 14 patients pre-treated with a beta-blocker who had documented coronary artery disease, stable angina pectoris, and > or = 2 mm of exercise-induced ST segment depression. For 2 days the patients received open-label amlodipine and then, according to a randomized, placebo-controlled, cross-over and double-blind protocol, they were treated with amlodipine or placebo, respectively, once a day for 3 weeks each. Exercise tests and blood sampling for plasma concentrations of amlodipine were performed at 8 and at 24 h after dosing on both days of acute testing as well as on day 18 of chronic treatment. During chronic treatment, when plasma concentrations fluctuated between 23.5 ng.ml-1 at 8 h and 14 ng.ml-1 at 24 h post-dosing, ST segment depression at an individually comparable workload was significantly decreased by 28% compared with placebo (P < 0.005) at both points in time. Increases in ischaemia-free workload capacity amounted to 76% (P < 0.005) and to 81% (P < 0.01) at 8 and at 24 h, respectively. The number of anginal attacks was reduced by 39% (P < 0.05). Conversely, after initial dosing, i.e. when plasma concentrations declined from 4.7 ng.ml-1 to 3.9 ng.ml-1, influences upon ischaemic parameters compared to control values were markedly less at 24 h as opposed to 8 h. There were no untoward side effects observed at any point in time.(ABSTRACT TRUNCATED AT 250 WORDS)