SINGLE-BLIND STUDY OF THE EFFECTS OF INTRAVENOUS DOLASETRON MESYLATE VERSUS ONDANSETRON ON ELECTROCARDIOGRAPHIC PARAMETERS IN NORMAL VOLUNTEERS

A single-blind, randomized, five-way crossover, safety and tolerabilit y trial was conducted to determine whether intravenous (i.v.) dolasetr on mesylate at varying single doses induces changes in ECG intervals i n healthy volunteers and to compare these changes with a single intrav enous dose of ondansetron or placebo. Thirty healthy male volunteers r eceived 1.2, 1.8, and 2.4 mg/kg i.v. dolasetron mesylate, 32 mg i.v. o ndansetron, and placebo on 5 separate days. ECGs were recorded at inte rvals during the 24 h after study drug administration. The changes in ECG intervals observed after dolasetron mesylate or ondansetron were a cute, transient, and asymptomatic. Dolasetron mesylate resulted in sli ght but statistically significant dose-related increases in heart rate (HR) and PR and QRS intervals (between h 0 and 4). A statistically si gnificant increase in QT(c) interval was detected with both dolasetron mesylate (2.4 mg/kg) and ondansetron. Ondansetron also produced a sli ght but statistically significant increase in JT interval and a decrea se in HR. These changes in ECG intervals were usually observed between h 0 and 4; all parameters returned to baseline within 8 h of treatmen t. The results demonstrate that both dolasetron mesylate and ondansetr on prolong the QT(c) interval. However, dolasetron mesylate predominan tly altered ECG parameters indicative of ventricular depolarization (Q RS duration), whereas ondansetron predominantly affected ventricular r epolarization as measured by a prolongation in the JT interval. Both d olasetron and ondansetron were well tolerated. The adverse event (AE) rate was 13.3% (4 of 30); all AE were of mild or moderate severity and were distributed across all dose arms.