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Accuracy and Reliability of Dosing Equations to Individualize Theophylline Treatment of Apnea of Prematurity
Author(s) -
BhattMehta Varsha,
Johnson Gary E.,
Donn Steven M.,
Spadoni Virginia,
Schork M. Anthony
Publication year - 1995
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1995.tb04360.x
Subject(s) - apnea of prematurity , theophylline , medicine , gestational age , dose , apnea , maintenance dose , correlation , loading dose , anesthesia , pregnancy , mathematics , biology , genetics , geometry
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 μg/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 × PNA in wks) + 5], and mg/kg/day = [(0.3 × 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 χ 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=0.0517) 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. Currently available equations for determining maintenance dosages of theophylline 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 determine if better ones can be developed.