The effect of cisapride on the corrected QT interval and QT dispersion in premature infants.
BACKGROUND
Cisapride is used frequently in premature neonates as a gastrointestinal prokinetic drug. Concerns exist, however, about its safety because of its effect on the QT interval. Premature infants could be at higher risk for side effects because of their immaturity. This prospective study investigated the pharmacokinetics of cisapride and its effects on corrected QT interval (QTc) and QT dispersion in premature infants.


METHODS
Electrocardiogram examination was performed just before and after 72 hours of treatment with cisapride (0.2 mg/kg per dose, four times daily) in 10 premature infants. Trough and anticipated peak plasma level of cisapride and norcisapride were quantified after 72 hours of treatment. Results were compared with a cohort of 41 term infants aged 0 to 3 months receiving cisapride treatment.


RESULTS
The QTc interval increased significantly from 423 ms to 461 ms after 72 hours of treatment (P = 0.0007). No effect was seen on QT dispersion (44.3 ms vs. 45.9 ms). The change in QTc interval was inversely related to postnatal age (R2 = 0.52; P = 0.02), whereas there was no correlation with gestational age or plasma levels of cisapride or norcisapride. Trough and anticipated peak plasma levels of cisapride and norcisapride were significantly higher in the premature infants compared with the term infants aged 0 to 3 months (P < 0.001).


CONCLUSIONS
Premature infants less than 1 month of age could be at higher risk for cardiac side effects of cisapride when used in the same dosage as in older infants. The daily dose should be reduced (0.1 mg/kg per dose, maximum four times daily), and the QTc interval should be monitored closely. The benefits and safety of cisapride in premature infants less than 1 month of age should be reconsidered.
Cools
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F
Academic Hospital, Free University of Brussels, Brussels, Belgium. Filip.Cools@az.vub.ac.be
Benatar
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Bougatef
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Vandenplas
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Y
D000367:Age Factors; D016022:Case-Control Studies; D020117:Cisapride / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D011446:Prospective Studies; D012449:Safety
D005765:Gastrointestinal Agents; D020117:Cisapride