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Author: Admin | 2025-04-28
Placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women 11,12. Ondansetron was tested at single doses of 8 mg and 32 mg infused intravenously over 15 minutes 11,12. At the highest tested dose of 32 mg, prolongation of the Fridericia-corrected QTc interval (QT/RR0.33=QTcF) was observed from 15 min to 4 h after the start of the 15 min infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 19.6 (21.5) msec at 20 min 11,12. At the lower tested dose of 8 mg, QTc prolongation was observed from 15 min to 1 h after the start of the 15-minute infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 5.8 (7.8) msec at 15 min 11,12. The magnitude of QTc prolongation with ondansetron is expected to be greater if the infusion rate is faster than 15 minutes 11,12. The 32 mg intravenous dose of ondansetron must not be administered 11,12. No treatment-related effects on the QRS duration or the PR interval were observed at either the 8 or 32 mg dose 11,12.An ECG assessment study has not been performed for orally administered ondansetron 11,12. On the basis of pharmacokinetic-pharmacodynamic modelling, an 8 mg oral dose of ondansetron is predicted to cause a mean QTcF increase of 0.7 ms (90% CI -2.1, 3.3) at steady-state, assuming a mean maximal plasma concentration of 24.7 ng/mL (95% CI 21.1, 29.0) 11,12. The magnitude of QTc prolongation at the recommended 5 mg/m2 dose in pediatrics has not been studied, but pharmacokinetic-pharmacodynamic modeling predicts a mean increase of 6.6 ms (90% CI 2.8, 10.7) at maximal plasma concentrations 11,12. In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time 10. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects 10. Ondansetron has no effect on plasma prolactin concentrations 10.Mechanism of actionOndansetron is a selective antagonist of the serotonin receptor subtype, 5-HT3
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