Background: Aminophylline is the medication use for treating apnea of prematurity and facilitating endotracheal extubation in preterm infants. The regimen of aminophylline therapy varies among institutions. However, the data on its safety are limited.

Objective: To compare rate of achieving theophylline therapeutic level and side effects between two regimens of aminophylline therapy in preterm infants.

Materials and Methods: Infants of gestational age less than 35 weeks and birthweight less than 2,000 grams who required aminophylline treatment or prophylaxis for apnea of prematurity were randomly allocated to one of two groups. Group 1 received an intravenous aminophylline loading dose at 5 mg/kg and then maintenance at 6 mg/kg/day. Group 2 received a loading dose at 8 mg/kg and maintenance at 4 mg/kg/day. Serum theophylline levels were measured at 2 to 3 hours after the loading dose and before the sixth maintenance dose. Apnea episodes, heart rate, and urine volume were closely monitored.

Results: Twenty-two infants were enrolled to each group. No differences of gestational age, birthweight, and indication were found among the two groups. At 2 to 3 hours after the loading dose, infants of group 2 had significantly higher rate of serum theophylline levels within the therapeutic range than group 1 (59.1% vs. 4.5%). This difference was not observed before the sixth maintenance dose. Frequency of apnea episodes was not different between the two groups. Only infants of group 2 had significant increases in heart rate after the loading dose. Both groups had significant increased in urine output volume after the loading dose.

Conclusion: The high loading-low maintenance regimen of aminophylline had advantage in achieving the therapeutic level more rapidly, whereas the low loading-high maintenance regimen had lower risk of tachycardia. Physicians should weigh between benefit and risk before choosing a regimen of aminophylline for preterm infants.

Keywords: Aminophylline, Theophylline, Apnea of prematurity