Theophylline is often used in infants, yet few studies have evaluated the serum concentrations achieved with currently recommended dosing guidelines. Two theophylline dosing regimens, a postnatal age (PNA) equation and the Federal Drug Administration (FDA) dosing guidelines, were retrospectively evaluated in a group of infants, postconceptional age (PCA) 31–96 weeks, with known theophylline clearances. Large variations in theophylline concentrations were observed for both dosing regimens. Mean ± SD projected steady-state theophylline serum concentrations, Css, were 17.7 ± 7.6 μg/ml with the PNA equation (n = 40) and 5.6 ± 2.9 μg/ml with the FDA guidelines (n = 52). Over one-third of Csswith the PNA equation were 20 μg/ml. Using the FDA guidelines, 40% of Csswere 5 μg/ml. The majority of infants 40 weeks PCA attained projected Css20 μg/ml (21.7 ± 5.1 μg/ml) with the PNA equation, but 5 μg/ml (4.3 ± 1.4 μg/ml) with FDA guidelines. An age-related bias was also observed for each dosing method. For the PNA equation, projected Csswere significantly higher in infants 40 weeks versus ≥40 weeks PCA (21.7 ± 5.1 versus 15.8 ± 7.9 μg/ml, p 0.01). For FDA guidelines, projected Csswere significantly lower in infants 40 weeks PCA versus older infants (4.3 ±1.4 versus 8.5 ± 4.3 μg/ml, p 0.001). Clinical application of currently accepted theophylline dosing guidelines for infants results in a high frequency of Css, which are potentially toxic or sub therapeutic. The wide variability and age-related bias may be attributed to using PNA as the primary basis for theophylline dosing. Since recent studies suggest PCA as the major determinant of theophylline clearance in infants, new theophylline dosing guidelines, which take into account gestational as well as PNA, need to be developed and evaluated.
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