When designing safe and effective dosing regimens for children, the first assumption is to aim for drug exposures similar to those observed in successfully treated adults. Therefore, correctly scaling pharmacokinetics (PK) to children is a key first step. While several factors may contribute to difference in PK between children and adults, body size alone explains most of the changes down to children of 3 years of age. Allometric scaling describes the nonlinear effect of body size on PK parameters. This nonlinearity explains why using the same mg/kg dose in children and adults is incorrect, and causes under-dosing. Allometric scaling is widely used in PK modelling, but it is not uncommon for ‘first guess’ paediatric dosing regimens to still incorrectly use constant mg/kg dosing. This is arguably due to the lack of accessibility of PK modelling results to clinicians. The objective of this work is to bridge this gap by proposing an intuitive and easy-to-use tool to assist researchers not conversant in PK modelling to design and evaluate paediatric dosing regimens.
The tool was designed using Microsoft Excel – chosen for its ubiquitousness and familiarity amongst clinicians – with easy steps to follow and results displayed in graphical form. The tool uses allometric scaling to adjust for the effect of body size on clearance and compares the expected exposure in terms of area under the concentration-time curve (AUC). Analysis of multiple drugs in a fixed-dose combination is possible, defining the separate amounts for each component and different tolerance ranges for the target exposure. Standard dosing weight-bands can be used, or boundaries can be customised to explore alternative approaches.
The implementation of the tool has been validated by assessing current paediatric dosing regimens. The outputs produced are closely in line with results from PK modelling and generally coherent with those obtained in confirmatory clinical trials. In particular, the doses predicted using the tool are more accurate than those obtained with the constant mg/kg approach.
The purpose of the tool is to assist in the design of clinical trials for dosing in paediatrics, and is meant as a first step, not a substitute to confirmatory studies. The use of this tool (and thus allometric scaling) for study design would represent a significant step ahead from the constant mg/kg paradigm, possibly leading to improvements in the efficacy of paediatric dosing trials.