Efficacy, safety, hemodynamic effects, and pharmacokinetics of high‐dose moricizine during short‐ and long‐term therapy

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 ⩾80% suppression of total ventricular ectopic depolarizations (P < 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 < 0.001), QRS interval increased 10% (P < 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. Clinical Pharmacology and Therapeutics (1987) 42, 201–209; doi: 10.1038/clpt.1987.133