Evaluation of the change in QTc interval in infants receiving cisapride therapy and plasma concentration monitoring

Introduction: Cisapride therapy has been associated with life threatening arrhythmias (Torsades de pointes) and prolongation of the QTc interval in adults and children. Cisapride exhibits a dose dependent class III anti-arrhythmic effect. Infants have a decreased ability to metabolize agents like cisapride due to immaturity of the cytochrome 450-3-A metabolic pathway and may be at risk for the development of serious cardiac arrhythmias secondary to elevated plasma concentrations. The hypothesis of this study was that cisapride use in infants is associated with an increased QTc (relative to baseline) and an elevated plasma concentration. Methods: This open-label prospective trial enrolled pediatric patients aged 4 days to 6 months who received oral cisapride at doses of at least 0.2 mg/kg/dose four times daily. A 12-lead ECG was performed at baseline and after 3 days of treatment. A plasma sample was collected on Day #3 of therapy and was analyzed for a cisapride plasma concentration. Results: Twelve patients were enrolled over four months (5 males and 7 females with mean age of 2mth (4 days-6 mth). Mean baseline QTc was 414 msec (range 366-442) and three days later QTc average was 424 msec (range 386-477). Mean absolute change in QTc was 10 msec (range 15-111). Six of nine patients had a non-detectable cisapride level. All three infants with detectable cisapride levels had a shortening of QTc interval ranging from 8 to 26 msec. Conclusion: The absence of a statistically significant change in mean QTc interval is tempered by the fact that 75% of the patients had non-detectable cisapride levels. This finding suggests absorption variability in infants which is well described for other agents used in this patient population. These results need to be addressed in future studies defining the effectiveness and ECG effects of cisapride in children.

Duke Scholars

Author Ronald Jay Kanter Pediatrics, Cardiology