Effects of terfenadine, astemizole and epinastine on electrocardiogram in conscious cynomolgus monkeys

We examined the effects of non-sedative histamine H-1 receptor antagonists on the electrocardiogram (ECG) in conscious cynomolgus monkeys. Terfenadine (3 mg kg(-1) h(-1), i.v.) and astemizole (0.3 and 1 mg kg(-1) h(-1), i.v.) caused significant time-dependent increases in the QT interval and QTc Baz ett (QTc). However, normal ECG forms were found during a 60-min infusion of epinastine (3 mg kg(-1) h-' i.v.), A higher dose of epinastine (10 mg kg(- 1) h-', i.v.) increased the QTc and PR interval only 5 min after the start of the infusion. The minimum plasma concentrations of terfenadine, astemizo le and epinastine which caused QTc prolongation were 85, 35 and over than 3 600 ng/ml, respectively. These drugs did not alter the PQ and QRS intervals and did not cause arrhythmia or atrioventricular block. Our results are co nsistent with the clinical observation that prolongation of QTc is caused b y terfenadine and astemizole but not by epinastine. Thus, measurement of QT e in cynomolgus monkey appears to be a useful approach for evaluating the p otential cardiotoxicity of histamine H-1, receptor antagonists. (C) 1999 El sevier Science B.V. All rights reserved.