Pharmacokinetics of Theophylline in Premature Infants with Apnea

Abstract

The pharmacokinetics of theophylline were studied in six premature infants (gestation: 31.7±3.1 weeks;birth-weight: 1062±304g).They received 5.5±0.4 mg/kg of aminophylline as a loading dose, and 1.5 mg/kg as a maintenance dose intravenously from average age of 6.1±3.3 days.Samples of blood were collected by heel-stick technique and plasma theophylline concentration was measured by high-performance liquid chromatography.The plasma data were analyzed by a two-compartment open model. The apparent volume of distribution was 0.662±0.107 1/kg, which was slightly larger than those of children and adults. However, the volume of central compartment (0.509±0.084/1/kg) was approximately two times larger.Plasma half-life for the elimination phase was 33.9±16.5 hours and body clearance was 16.9±7.4ml/kg/hr. Theophylline elimination in premature infants was extremely slower than that in children and adults, and highly variant.The results indicated that 6.6 mg/kg of aminophylline as a loading dose and 0.17 mg/kg/hr as a maintenance dose would generate a mean plasma concentration of 8μg/ml.Since theophylline elimination is highly variant and increases with maturation of infants, the dosage should be adjusted individually by monitoring the plasma theophylline concentration.