Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Thomas P. Green; Helen J. Binns; Huali Wu; Adolfo J. Ariza; Eliana M. Perrin; Maheen Quadri; Christoph P. Hornik; Michael Cohen-Wolkowiez

doi:10.1111/cts.12896

Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Thomas P. Green^*, Helen J. Binns, Huali Wu, Adolfo J. Ariza, Eliana M. Perrin, Maheen Quadri, Christoph P. Hornik, Michael Cohen-Wolkowiez

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Obesity is a prevalent childhood condition and the degree of adiposity appears likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. We undertook these studies to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. We examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. Additionally, we conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. BF% was correlated with body mass index (BMI), but was highly variable among both children with healthy body weights and those with obesity. Bio-impedance and several demographically derived techniques produced mean estimates of BF% that differed from dual x-ray absorptiometry by < 1% (accuracy) and a SD of 5% or less (precision). Simulation studies confirmed that when the differences in precision among the several methods were small compared with unexplained between-subject variability of a PK parameter, the techniques were of similar value in assessing the contribution of BF%, if any, as a covariate for that PK parameter. The combination of sex and obesity stage explained 68% of the variance of BF% with BMI. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.

Original language	English (US)
Pages (from-to)	509-517
Number of pages	9
Journal	Clinical and Translational Science
Volume	14
Issue number	2
DOIs	https://doi.org/10.1111/cts.12896
State	Published - Mar 2021

Funding

This work was funded under National Institute of Child Health and Human Development (NICHD) contract HHSN275201000003I for the Pediatric Trials Network (PI Danny Benjamin). H.W. receives salary support for research from the National Institutes of Health (NIH) Clinical and Translational Science Award (5UL1TR001117-05). C.P.H. receives salary support for research from the NICHD (K23HD090239) and the US government for his work in pediatric and neonatal clinical pharmacology (contract HHSN267200700051C, PI D. Benjamin under the Best Pharmaceuticals for Children Act). M.C.-W. receives support for research from the NIH (5R01-HD076676 and HHSN275201000003I), National Institute of Allergy and Infectious Diseases (HHSN272201500006I), US Food and Drug Administration (1U18-FD006298), and Biomedical Advanced Research and Development Authority (HHSO100201300009C). The design and conduct of the study, the interpretation of data, the preparation, review, and decision to submit the manuscript were all solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This work was funded under National Institute of Child Health and Human Development (NICHD) contract HHSN275201000003I for the Pediatric Trials Network (PI Danny Benjamin). H.W. receives salary support for research from the National Institutes of Health (NIH) Clinical and Translational Science Award (5UL1TR001117‐05). C.P.H. receives salary support for research from the NICHD (K23HD090239) and the US government for his work in pediatric and neonatal clinical pharmacology (contract HHSN267200700051C, PI D. Benjamin under the Best Pharmaceuticals for Children Act). M.C.‐W. receives support for research from the NIH (5R01‐HD076676 and HHSN275201000003I), National Institute of Allergy and Infectious Diseases (HHSN272201500006I), US Food and Drug Administration (1U18‐FD006298), and Biomedical Advanced Research and Development Authority (HHSO100201300009C). The design and conduct of the study, the interpretation of data, the preparation, review, and decision to submit the manuscript were all solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry, Genetics and Molecular Biology
General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cts.12896

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title = "Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children",

abstract = "Obesity is a prevalent childhood condition and the degree of adiposity appears likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. We undertook these studies to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. We examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. Additionally, we conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. BF% was correlated with body mass index (BMI), but was highly variable among both children with healthy body weights and those with obesity. Bio-impedance and several demographically derived techniques produced mean estimates of BF% that differed from dual x-ray absorptiometry by < 1% (accuracy) and a SD of 5% or less (precision). Simulation studies confirmed that when the differences in precision among the several methods were small compared with unexplained between-subject variability of a PK parameter, the techniques were of similar value in assessing the contribution of BF%, if any, as a covariate for that PK parameter. The combination of sex and obesity stage explained 68% of the variance of BF% with BMI. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.",

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Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Abstract

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