Lack of effect of respiratory syncytial virus infection on theophylline disposition in children.

Conflicting reports raise a question about decreased plasma clearance (Clp) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Clp 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 Clp 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 Clp were calculated. An age-matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Clp 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 Clp and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Clp; this did not affect findings regarding RSV infection. Theophylline Clp 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.

Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis in children.

Ibuprofen was evaluated as an antipyretic agent in 178 children (aged 3 months to 12 years) to compare dosage (5 vs 10 mg/kg), establish absolute efficacy (with a placebo control group), determine relative efficacy (ibuprofen vs acetaminophen), evaluate maximum efficacy, and identify potential confounding variables. Ibuprofen 5 mg/kg was minimally effective in children less than 6 years of age who had an initial temperature of at least 38.8 degrees C (101.9 degrees F). Ibuprofen 10 mg/kg was more effective for febrile children. The area under the curve for temperature (or change in temperature) captured the net effect of each drug and provided the best estimate for efficacy comparison during a defined period. A linear correlation between initial temperature and measures of efficacy was observed. A twofold increase in efficacy was observed for children with an initial temperature less than 38.8 degrees C. A similar effect was noted for each treatment group. Age was also found to have confounding effects on antipyretic response. A complex interaction between antipyretic response, initial temperature, and age raises questions about the pharmacodynamics of the antipyretic response. We conclude that the most important variable in antipyretic study design is initial temperature. The influence of initial temperature on the magnitude of the response to an antipyretic drug is a previously unappreciated finding with potential impact on pharmacodynamic investigations of antipyretic medications. We describe this finding as nonlinear pharmacodynamics.

Absence of a pharmacokinetic interaction between chloramphenicol and acetaminophen in children.

The pharmacokinetics of chloramphenicol (CAP; administered intravenously as chloramphenicol succinate, CAPS) was studied in 26 acutely ill febrile children 3 to 58 months of age who either did (n = 18) or did not (n = 8) receive acetaminophen (APAP) for antipyresis. CAP pharmacokinetics were evaluated after the first dose and at steady state. CAP serum levels were quantitated by high-performance liquid chromatography. There were no significant differences between groups (APAP vs non-APAP) or between first dose and steady-state evaluations for the elimination rate constant, serum half-life, apparent volume of distribution, and serum clearance of CAP. Likewise, there were no statistically significant differences when the APAP group was evaluated according to the presence or absence of APAP in serum before the first dose of CAP. Elimination of CAP in subjects with serum CAPS level less than 1 microgram/ml was similar in the first dose and steady-state evaluations and in the APAP and non-APAP groups. The presence or absence of CAPS or APAP did not affect the estimation of CAP elimination. Thus a pharmacokinetic interaction between CAP and APAP was not demonstrated in acutely ill febrile children during concomitant therapy.