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\begin{document}

\title{Use of population pharmacokinetic-pharmacodynamic modelling to inform
antimalarial dose optimisation in infants}



\author[1]{Clifford  Banda }%
\author[2]{Joel Tarning}%
\author[3]{Karen Barnes }%
\affil[1]{Malawi-Liverpool-Wellcome Trust Clinical Research Programme}%
\affil[2]{University of Oxford}%
\affil[3]{Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.}%


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  \date{June 17, 2024}


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\begin{abstract}
Infants bear a significant malaria burden but are usually excluded from
participating in early dose optimisation studies that inform dosing
regimens of antimalarial therapy. Unlike older children, infants'
exclusion from early-phase trials has resulted in limited evidence to
guide accurate dosing of antimalarial treatment for uncomplicated
malaria or malaria preventive treatment in this vulnerable population.
Subsequently, doses used in infants are often extrapolated from older
children or adults, with the potential for under or overdosing.
Population pharmacokinetic-pharmacodynamic (PK-PD) modelling, a
quantitative methodology that applies mathematical and statistical
techniques, can aid the design of clinical studies in infants that
collect sparse pharmacokinetic data as well as support the analysis of
such data to derive optimised antimalarial dosing in this complex and
at-risk yet understudied subpopulation. In this review, we reflect on
what PK-PD modelling can do in programmatic settings of most
malaria-endemic areas and how it can be used to inform antimalarial dose
optimisation for preventive and curative treatment of uncomplicated
malaria in infants. We outline key developmental physiological changes
that affect drug exposure in early life, the challenges of conducting
dose optimisation studies in infants, and examples of how PK-PD
modelling has previously informed antimalarial dose optimisation in this
subgroup. Additionally, we have discussed the limitations and gaps of
PK-PD modelling when used for dose optimisation in infants and best
practices for using population PK-PD methods in this subgroup.%
\end{abstract}%



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\verb`Use of modelling to inform antimalarial dose optimisation in infants.docx`  available at \url{https://authorea.com/users/361448/articles/672015-use-of-population-pharmacokinetic-pharmacodynamic-modelling-to-inform-antimalarial-dose-optimisation-in-infants}

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