Pharmacokinetics And Pharmacodynamics Of Theophylline In Premature Infants

Apnea of prematurity (AOP) is a common disease in neonates, especially those born at less than 34 weeks' gestational age. Its incidence depends on neonates' gestational age and weight. Theophylline, a methylxanthine, is the most extensively used drug to treat idiopathic AOP in China. The range of theophylline serum concentrations for effective treatment is narrow (6～12 mg·L-1). The theophylline serum levels may fluctuate widely due to various reasons. The pharmacokinetics of theophylline in term and near term neonates has been studied in China.The aim of the study is to estimate the pharmacokinetic parameters of theophylline in premature infants, evaluate the pharmacodynamics of theophylline in treatment of idiopathic apnea of prematurity and detect the adverse reactions to guide rational drug use in clinical therapy.Firstly the pharmacokinetics of theophylline was examined in eleven premature infants. The drug serum concentration was determined by fluorescence polarization immunoassay. Theophylline had a half-life time of (43.4±33.2) h, an apparent volume of distribution of (0.682±0.113) L·g-1, and a body clearance of (14±6) mL·h-1·kg-1. The pharmacokinetics of theophylline in premature infants was significantly different form that in mature infants.Secondly we evaluated the pharmacodynamics of theophylline to treat idiopathic AOP in twenty-one premature infants.65.8% theophylline serum concentrations ranged between (3～6) mg·L-1. Cure rate of AOP was 81.0%. Apnea rate decreased significantly during theophyline administration. Theophylline appeared to have similar effects on apnea as that of caffeine. There was no significant decrease in oxygen consumption during theophylline administration. The most common adverse reaction was urorrhagia.In conclusion, the pharmacokinetics of theophylline in premature infants is significantly different from that in mature infants, and there is large difference among the individuals. When theophylline serum concentrations range between (3～6) mg·L-1, the rate of idiopathic AOP is also reduced. The adjustments of dosage regimen in premature infants should be made based on monitoring the serum concentration.