THEOPHYLLINE PHARMACOKINETICS IN THE PREMATURE INFANT WITH PRIMARY APNEA

Abstract

Although it is known that activity of cytochrome P450 1A2 in premature infants is lower than in adults and children, it is difficult to obtain enough blood samples of premature infants to monitor the pharmacokinetics of theophylline. We evaluated theophylline pharmacokinetics in pramature infants with primary apnea by measuring theophylline urinary metabolites and serum conceutrations and assessed the relationships between pharmacokinetics and characteristics of infants including posthatal age and postconceptional age. Changes of theophylline clearance and urine metabolies were investigated in 24 cases of 20 premature infants receiving theophylline therapy at a steady state. The infants gestational ages ranged from 24.7 to 37.0 weeks: postnatal from 3 to 71 days and postconceptional from 29.9 to 38.4 weeks. Total clearance and renal clearance were calculated as 0.251±0.072 ml/kg/min and 0.091±0.047ml/kg/min, respectively Percentage of renal clearance was 36.3%. We concluded that total clearance of theophylline (p<0.005) and renal clearance (p<0.001) correlated with postnatal age and not with postconceptional age in premature infants of less than two months old.