Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography
A Benatar1, A Feenstra, T Decraene
1Departments of Pediatric Cardiology and Pediatric Gastroenterology, Academic Hospital, Free University of Brussels, 101 Laarbeeklaan, 1090 Brussels, Belgium.
Insights
Infants under 3 months treated with cisapride showed prolonged QTc intervals, indicating age-dependent pharmacokinetics. Careful prescription and ECG monitoring are advised for this age group to mitigate potential cardiac risks.
Area of Science:
- Pediatric Pharmacology
- Cardiology
- Clinical Pharmacy
Background:
- Previous reports linked cisapride therapy to QTc prolongation and cardiac arrhythmia in children.
- A lack of pharmacokinetic correlation necessitated further investigation into cisapride's effects in infants.
Purpose of the Study:
- To evaluate the relationship between cisapride plasma concentrations, QT interval, and cardiac rhythm in infants.
- To investigate age-dependent cisapride pharmacokinetics and its association with QTc interval changes.
Main Methods:
- A prospective study involving 211 infants (84 cisapride-treated, 127 controls) aged 1 week to 13.5 months.
- Continuous ECG monitoring during polysomnography, with QT intervals and heart rate measured hourly.
- Cisapride plasma concentrations and serum electrolytes measured, alongside 12-lead ECG post-administration.
Main Results:
- Cisapride plasma concentrations were higher in infants younger than 3 months.
- Infants under 3 months treated with cisapride exhibited significantly longer QTc intervals compared to controls.
- No significant difference in heart rate or observed arrhythmias between treated and control groups.
Conclusions:
- Age-dependent cisapride pharmacokinetics in infants under 3 months correlate with QTc interval changes.
- Altered cisapride metabolism in younger infants may contribute to increased QTc intervals.
- Judicious cisapride use and ECG monitoring are recommended for infants younger than 3 months.
Background:
Reported QTc prolongation associated with cardiac arrhythmia in a small number of children undergoing cisapride therapy and lack of pharmacokinetic correlation provided the impetus for this prospective study. The authors evaluated the relation between cisapride plasma concentrations, the electrocardiographic QT interval, and cardiac rhythm in infants undergoing routine 8-hour polysomnography.
Methods:
A total of 211 infants were enrolled: 84 (17 born prematurely) undergoing cisapride therapy for at least 4 days for suspected gastroesophageal reflux and 127 controls (10 born prematurely), aged between 1 week and 13.5 months. Infants underwent continuous bipolar limb lead I recording during routine 8-hour polysomnography. QT intervals and heart rate were measured at hourly intervals. The morning after polysomnography, 12-lead electrocardiography was performed (1 hour after cisapride administration). Cisapride plasma concentrations were determined immediately before and 1 to 2 hours after administration. Serum electrolyte concentrations were measured.
Results:
The administered cisapride dose ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg. kg-1. d-1. Cisapride plasma concentrations were significantly higher in infants younger than 3 months of age. Cisapride-treated infants younger than 3 months of age had longer QTc intervals compared with age-matched controls. Heart rate was similar for cisapride-treated and control infants. No arrhythmia or atrioventricular conduction abnormalities were observed.
Conclusions:
At comparable doses of cisapride and comparable plasma concentrations, the QTc was significantly higher in infants younger than 3 months of age. This confirms age-dependent cisapride pharmacokinetics in the first 10 to 12 weeks strongly correlated with changes in body weight and may also suggest an altered ability of infants younger than 3 months of age to metabolize cisapride. The clinical significance and risk of the increased QTc interval is unclear. Cisapride should be judiciously prescribed in infants younger than the age of 3 months and electrocardiography should be performed before and during therapy.
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