Prospective evaluation of two dosing equations for theophylline in premature infants

To evaluate prospectively the ability of two equations that we previously derived to predict maintenance theophylline dosages that provide a serum theophylline concentration (STC) of 8 micrograms/ml, the midtherapeutic range for treating apnea of prematurity; and to determine the number of further dosage adjustments and STC determinations required to achieve the target concentration in infants in whom it was not achieved initially.

Prospective study.

A 37-bed neonatal intensive care unit.

Fifty-four infants 27-34 weeks' gestational age requiring intravenous hydrous aminophylline.

Patients received a loading dose of 6 mg/kg intravenous aminophylline, followed by a maintenance dosage calculated using one of the two derived equations. The basis for equation selection was the gestational age of the patient.

Patients were stratified into two age groups: 27-30 weeks' gestational age (34 infants) and 31-34 weeks' gestational age (20 infants). The overall success rate for both equations in achieving the target concentration was 74%. When infants were stratified by gestational age, those dosed by Equation 1 had a 76% success rate and those dosed by Equation 2 had a 65% success rate. Overall, 14 of 54 infants received an average of 1.2 dosage adjustments. This represents more than a 50% reduction in the number of adjustments made before introduction of these equations.

The ability of our previously derived equations to produce an STC within the midtherapeutic range for treating apnea of prematurity was demonstrated in the majority of patients studied (74%). Further, the number of subsequent dosage adjustments required to attain the target STC in infants who had failed to achieve this STC initially was significantly less than using older, more traditional regimens.