LACK OF EFFECT OF RESPIRATORY SYNCYTIAL VIRUS-INFECTION ON THEOPHYLLINE DISPOSITION IN CHILDREN

Conflicting reports raise a question about decreased plasma clearance (Cl(p)) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Cl(p) in children infected with respiratory syncytial virus (RSV). Two pharmacokinetic approaches were applied to a one-compartment open model to fit theophylline concentrations during 83 hospitalizations of 76 children, 6 to 48 months of age, who received intravenous theophylline therapy and were tested for RSV infection. Iterative linear regression analyses of all theophylline data were used to estimate apparent volume of distribution, elimination rate constant, plasma half-life, and Cl(p) in 39 of the hospitalizations. When insufficient data were available to distinguish apparent volume of distribution and elimination rate constant (n = 44), steady-state estimates of Cl(p) were calculated. An age-matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Cl(p) was similar in 29 matched RSV-infected and -uninfected pairs (1.32 +/- 0.14 and 1.25 +/- 0.05 ml/kg per minute, respectively), as were other pharmacokinetic values. Unexpectedly, a significant, inverse linear relationship was found for Cl(p) and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Cl(p); this did not affect findings regarding RSV infection. Theophylline Cl(p) was not decreased in RSV-infected children. Current theophylline dosing recommendations for young children infected with RSV should not be altered, but careful monitoring of plasma theophylline levels should be continued.