ACCURACY AND RELIABILITY OF DOSING EQUATIONS TO INDIVIDUALIZE THEOPHYLLINE TREATMENT OF APNEA OF PREMATURITY

Apnea of prematurity is associated with high morbidity and mortality. Treatment generally includes supplemental oxygen and rheophylline or c affeine. The half-life of theophylline is prolonged in newborns becaus e of their immature cytochrome P-450 system, and there is considerable variation in the drug's metabolism in infants. We compared the accura cy, precision, and reliability of two equations that use postnatal age (PNA) to determine a maintenance dosage of theophylline with a standa rd maintenance dosage (SMD) that produced a steady-state serum theophy lline concentration (STC) of 8 mu g/ml for apnea of prematurity in 46 infants less than 34 weeks' gestational age (GA) and less than 36 week s' 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 determi ned and analyzed by chi(2). The SMD did not correlate with the mainten ance dosages calculated by equations 1 and 2 (r=0.296 and 0.296, p>0.0 5 in both cases). Multiple linear regression of SMD versus GA, PNA, an d PCA was not significant (r=0.33, p=0.32). After stratifying data bas ed on GA and performing correlation analysis of SMD versus PNA, a weak but significant correlation (r=0.42, p=0.0517) was found for infants with GA between 31. and 34 weeks. Poor correlation was found between S MD versus PNA for infants 27-30 weeks' GA. Two new equations of the be st fit line were generated using the same data. Currently available eq uations for determining maintenance dosages of rheophylline in infants and children are not reliable for premature newborns, in whom two new equations based on GA and PNA have been developed. The equations will be evaluated for their utility, and employed to accrue data to determ ine if better ones can be developed.