title: 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.
abstract: 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)
authors.affiliation: Department of Cardiology, German Heart Centre, Munich.
authors.forename: G
authors.initials: G
authors.lastname: Lehmann
authors.forename: G
authors.initials: G
authors.lastname: Reiniger
authors.forename: A
authors.initials: A
authors.lastname: Beyerle
authors.forename: W
authors.initials: W
authors.lastname: Rudolph
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D017311:Amlodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy*; D003327:Coronary Disease / Q000188:drug therapy; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans
chemical_list: D000319:Adrenergic beta-Antagonists; D017311:Amlodipine