Theophylline pharmacokinetics in premature infants with apnea

The pharmacokinetics of theophylline were examined in eight low-birth-weight infants (gestation: 26-32 weeks; birth-weight: 887-1,480 gm), who received the drug for treatment of primary apnea. The drug was assayed by high pressure liquid chromatography. The final dosage was 1 to 3 mg/kg/6 hour at 25 to 57 days of age. At that time, theophylline had a prolonged half-life ranging from 13 to 29 hours, a relatively large volume of distribution of 0.65 to 2.86 l/kg, and a small body clearance of 23 to 68 ml/hr/kg. The extremely slow and variable elimination of theophylline must be considered in treatment of apneic infants. The initial dosage regimen suggested is a loading dose of 6 mg/kg and a maintenance dose of 2 mg/kg/ 12 hours, with adjustments made based on monitoring of the serum concentration and on an increased biotransformation capability as maturation occurs.