NEW YORK (Reuters Health) – The World Health Organization (WHO) pediatric dosing tool has been updated to account for the non-linear effect of body size and maturation.
“The first version of the dosing tool assumed a linear relationship between body weight and dose and targeted constant mg/kg dosing across weight bands, thus leading to under-dosing in young children,” Dr. Paolo Denti of the University of Cape Town, South Africa, and colleagues explain in The Lancet Child & Adolescent Health.
“The revised tool represents a substantial improvement because it addresses the issue of systematically underexposing children when using a constant mg/kg approach,” they write.
Using the tool to design pediatric dosing regimens represents “an important step forward from the constant mg/kg paradigm,” they say.
“We aimed to make it intuitive and user-friendly for non-pharmacokinetic experts to visualize the expected exposure across WHO weight bands and assess the likelihood of supratherapeutic or subtherapeutic exposures, for both novel single drugs and fixed-dose combinations,” they explain.
“The tool can provide a prediction of exposures, relative to adults, for drugs even when pediatric data are not available,” they say. “For younger children, the tool allows for the additional effect of maturation on drug clearance, if information for that specific drug is available.”
Dr. Denti and colleagues emphasize that, despite the adjustments accounting for allometry and maturation, caution should be exercised when interpreting the predicted relative exposures in younger children, especially infants younger than one year and neonates younger than 28 days old.
“The new tool is meant to be used as a first evaluation step when information about a drug is scarce; the tool is not a substitute for confirmatory studies.”
A full description of the tool, including the pharmacokinetic principles on which it is based, is available in appendix 2 of the online article.
SOURCE: https://bit.ly/3vDxEjr The Lancet Child & Adolescent Health, online October 19, 2021.
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