Elsevier

The Journal of Pediatrics

Volume 119, Issue 5, November 1991, Pages 803-811
The Journal of Pediatrics

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

https://doi.org/10.1016/S0022-3476(05)80307-5Get rights and content

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°C (101.9°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°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.

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    Despite the lack of statistical difference in these parameters between the two doses, the authors concluded that, based on three other AUC endpoints, including the AUC of the change in temperature required to reduce baseline to normal versus time (AUC ΔTempn), the 10-mg/kg dose was more effective. Nevertheless, when considering the low-temperature group, even AUC ΔTempn values were not significantly different between the two tested doses.27 Such apparent divergence between predicted and observed dose–response relationship might be because of the greater sample size in each simulated dose group than in the reported clinical trials as well as an underestimation of the variability in the simulations.

  • Dosing and antipyretic efficacy of oral acetaminophen in children

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    Six studies used doses of <10 mg/kg; 9 studies, 10 mg/kg; 12 studies, >10–<15 mg/kg; 13 studies, 15 mg/kg; and 2 studies, 20–30 mg/kg. Table V17–57 additionally lists ΔTempmax by time following acetaminophen administration. Figure 3 shows mean ΔTemp for the 5 major dose ranges by time period following drug administration.

  • Regulatory review of acetaminophen clinical pharmacology in young pediatric patients

    2012, Journal of Pharmaceutical Sciences
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    Studies with mean data only or with the lowest pediatric patient age of 2 years were not included. A total of 15 studies fit in this criteria and were included.33,38,42,43,45–55 The weighted sum of temperature reduction for 6 h (WSTD6) was calculated as the fever reduction endpoint.

  • FEVER: PATHOGENESIS AND TREATMENT

    2009, Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Sixth Edition
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*

Supported in part by Bristol-Myers Products, Hillside, N.J.

Presented in part at the XIth International Congress of Pharmacology, Amsterdam, The Netherlands, July 1–6, 1990.

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