Efficacy, safety, hemodynamic effects, and pharmacokinetics of high-dose moricizine during short- and long-term therapy |
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Authors: | D M Salerno P J Sharkey G A Granrud R W Asinger M Hodges |
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Abstract: | Moricizine, 15 mg/kg, was given to 10 patients with frequent ventricular ectopic depolarizations, eight of whom had previously been treated unsuccessfully with antiarrhythmic drugs. A single-blind inpatient study was followed by therapy for up to 6 months. Two patients developed aggravation of arrhythmia during inpatient therapy. Of the eight patients who completed the inpatient study, seven achieved greater than or equal to 80% suppression of total ventricular ectopic depolarizations (P less than 0.001). During inpatient therapy the mean of the individual patients' suppression of total ventricular ectopic depolarizations was 87.9%, paired ventricular beats 99.3%, nonsustained ventricular tachycardia 99.6%, and premature atrial contractions 89.0%. Suppression was maintained during long-term therapy. The PR interval increased 27% (P less than 0.001), QRS interval increased 10% (P less than 0.0001), QTc increased 1% (P not significant), and JTc decreased 2% (P not significant). Heart rate, blood pressure, and left ventricular performance at rest and exercise were unchanged by moricizine. Moricizine half-life was 9.2 +/- 3.4 hours. Plasma levels of moricizine decreased after 10 days of therapy, suggesting induction of metabolic enzyme systems. |
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