Intrauterine Growth Retardation is a Risk Factor for Cisapride-Induced QT Prolongation in Preterm Infants
Clinical Pharmacology and Drug Studies
Background Cisapride is a possible cause of potentially life threatening QT prolongation.
Aims We investigated these cardiac side effects in premature infants, mainly in relation to fetal growth.
Patients Forty six preterms (mean birth weight 1.350 g, mean post conceptional age 31 weeks) were studied. Thirty one of them were appropriate for gestational age (AGA) and 15 were small for gestational age (SGA). Cisapride was randomly administered at a 0.3 mg/kg or 0.6 mg/kg daily dose. Fifty preterms (15 SGA/35 AGA) not treated with Cisapride were used as control group.
Methods A pre-treatment ECG was performed and the QT-corrected (Bazzet’s formula) intervals were compared with the in-treatment values (normal values ≤440 mseconds). In the control group two different ECG were performed with a timing similar to the treated group (mean interval 5 days).
Results and Conclusions No patients showed clinical evidence of drug toxicity. In the small for gestational age group, both baseline QTc (mean 397; range 370–420 ms) and in-treatment QTc (mean 410 range 360–500 ms) were significantly higher than those found in the appropriate for gestational age group (mean 386, range 360–420 ms; mean 396, range 370–420 ms, respectively). This difference was found also in the first ECG of the control group. Moreover the mean QTc lengthening during treatment was significantly higher in small for gestational age group than in the appropriate for gestational age group.
Three infants showed a rise in the QTc interval above the value of 440 ms and all were SGA (p = 0.03). No significant correlation was found between birth weight or gestational age and the change in QTc values during Cisapride treatment in the appropriate for gestational age group. Intrauterine growth retardation is a major risk factor for Cisapride-induced QT prolongation in preterm infants.
Key Wordscisapride preterms QT corrected interval small for gestational age
neonatal intensive care units
small for gestational age
appropriate for gestational age
isoform 3A4 of the cytochrome P-450
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