Accuracy and reliability of dosing equations to individualize theophylline treatment of apnea of prematurity

Pharmacotherapy. 1995 Mar-Apr;15(2):246-50.


Apnea of prematurity is associated with high morbidity and mortality. Treatment generally includes supplemental oxygen and theophylline or caffeine. The half-life of theophylline is prolonged in newborns because of their immature cytochrome P-450 system, and there is considerable variation in the drug's metabolism in infants. We compared the accuracy, precision, and reliability of two equations that use postnatal age (PNA) to determine a maintenance dosage of theophylline with a standard maintenance dosage (SMD) that produced a steady-state serum theophylline concentration (STC) of 8 micrograms/ml for apnea of prematurity in 46 infants less than 34 weeks' gestational age (GA) and less than 36 weeks' postconceptional age (PCA). The two equations were mg/kg/day = [(0.2 x PNA in wks) + 5], and mg/kg/day = [(0.3 x PNA in wks) + 8]. Their reliability to predict the SMD was determined by correlation analysis. The precision and accuracy with which they predicted SMD were determined and analyzed by chi 2. The SMD did not correlate with the maintenance dosages calculated by equations 1 and 2 (r = 0.296 and 0.296, p > 0.05 in both cases). Multiple linear regression of SMD versus GA, PNA, and PCA was not significant (r = 0.33, p = 0.32). After stratifying data based on GA and performing correlation analysis of SMD versus PNA, a weak but significant correlation (r = 0.42, p = 0.517) was found for infants with GA between 31 and 34 weeks. Poor correlation was found between SMD versus PNA for infants 27-30 weeks' GA. Two new equations of the best fit line were generated using the same data.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Age Factors
  • Apnea / drug therapy*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Prospective Studies
  • Reproducibility of Results
  • Statistics as Topic
  • Theophylline / administration & dosage*
  • Theophylline / blood
  • Theophylline / therapeutic use


  • Theophylline