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\begin{document}

\title{Physiologically-based pharmacokinetics modelling of Semaglutide in
children and adolescents with healthy and obese body weights}



\author[1]{Thayná Machado}%
\author[1]{Thiago Honorio}%
\author[2]{Thaisa Domingos}%
\author[1]{Dailane Candido de Paula}%
\author[1]{Lúcio Cabral}%
\author[1]{Carlos Rodrigues}%
\author[1]{Alessandra Souza}%
\author[1]{Bárbara Abrahim-Vieira}%
\affil[1]{Universidade Federal do Rio de Janeiro}%
\affil[2]{BIODATA Computing Services \& Consulting}%


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  \date{March 14, 2025}


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\begin{abstract}
Aim: Develop PBPK models of semaglutide to estimate the pharmacokinetic
profile for subcutaneous (SC) injections in children and adolescents
with healthy and obese body weights. Methods: Pharmacokinetic modeling
and simulations of semaglutide SC injections were performed using the
Transdermal Compartmental Absorption \& Transit (TCAT) model
implemented in GastroPlus v.9.5 modules. A PBPK model of semaglutide
was developed and verified in the adult population, by comparing the
simulated plasma exposure with the observed data, and further scaled to
the pediatric populations with normal and obese body weight. Results:
The Semaglutide PBPK model was successfully developed in adults and
scaled to the pediatric population. Our P-PBPK simulations indicated a
significant increase in Cmax values for the 10-14 years pediatric
population with healthy body weights, which was higher than the observed
values in adults at the reference dose. Since gastrointestinal adverse
events are related to increased semaglutide exposure, peak
concentrations outside the target range may represent a safety risk for
this pediatric age group. Besides, PBPK models indicated that body
weight was inversely related to semaglutide exposure in children and
adolescents, which is in line with the results observed in population
pharmacokinetic studies in adults. Conclusion: Due to the absence of
semaglutide pharmacokinetic data for the pediatric population, these
PBPK models will aid in the development of dosing regimens and sampling
times. Thus, increasing the efficiency of future pediatric clinical
trial studies which can be replaced or improved by PBPK models.%
\end{abstract}%



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