Predicting Pediatric Age-Matched Weight and Body Mass Index
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The empirical scaling from adult to pediatric using allometric size adjustments based on body weight continued to be the mainstream method for pediatric dose selection. Due to the flexibility of a polynomial function to conform to the data trend, an empirical function for simulating age-matched weight and body mass index by gender in the pediatric population is developed by using a polynomial function and a constant coefficient to describe the interindividual variability in weight. A polynomial of up to fifth order sufficiently described the pediatric data from the Center for Disease Control (CDC) and the World Health Organization (WHO). The coefficients of variation to describe the variability were within 17%. The percentages of the CDC simulated weights for pediatrics between 0 and 5 years that fell outside the WHO 90% and 95% confidence boundaries were well within the expected percentage values, indicating that the CDC dataset can be used to substitute for the WHO dataset for the purpose of pediatric drug development. To illustrate the utility of this empirical function, the CDC-based age-matched weights were simulated and were used in the prediction of the concentration–time profiles of tenofovir in children based on a population pharmacokinetic model whose parameters were allometrically scaled. We have shown that the resulting 95% prediction interval of tenofovir in newborn to 5 years of age was almost identical whether the weights were simulated based on WHO or CDC dataset. The approach is simple and is broadly applicable in adjusting for pediatric dosages using allometry.
KEY WORDSAge Allometry BMI Pediatric Weight
- 16.WHO. Working Group on Infant Growth. An evaluation of infant growth. Geneva: World Health Organization; 1994.Google Scholar
- 17.Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. CDC growth charts for the United States: methods and development. Vital Health Stat. 2002;11(246):1–190.Google Scholar
- 20.Growth chart datasets from both the CDC and WHO are downloadable from http://www.cdc.gov/growthcharts/who_charts.htm
- 22.Sy SK, Innes S, Derendorf H, Cotton MF, Rosenkranz B. Estimation of intracellular concentration of stavudine-triphosphate in HIV-infected children given the reduced dose of 0.5 mg/kg twice daily. Antimicrob Agents Chemother. 2013. doi: 10.1128/AAC.01717-13.
- 23.Strougo A, Eissing T, Yassen A, Willmann S, Danhof M, Freijer J. First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development. J Pharmacokinet Pharmacodyn. 2012;39(2):195–203. doi: 10.1007/s10928-012-9241-9.PubMedCrossRefPubMedCentralGoogle Scholar