Human development of an individual from a fertilized ovum to maturity alters the body anatomy and physiology. Changes of
size and function, from birth onwards, cause significant alterations in the pharmacokinetics (PK) of drugs and subsequently their response
pharmacodynamics (PD) in infants and children from those in adults. During the last three decades, hundreds of mechanistic and clinical
pharmacology studies have been conducted to investigate the age-mediated changes of absorption, distribution, metabolism and excretion
processes of drugs, which subsequently affect the pharmacology response and the safety in pediatric patients compared to adults. The
practice of determining pediatric dose based on simplistic scaling of an adult dose assuming linear relationship between postnatal age and
body weight or surface area that may lead to under prediction of therapeutic dose or over prediction of the dose is now under scrutiny.
By understanding the disposition mechanism of therapeutic agents thoroughly, their potential drug interactions and their PK/PD relationships
can be better determined in pediatric populations. As such, dosing regimens can be estimated based on actual clearance and exposure
and not just by simplistic scaling of an adult dose. Accurate prediction of clearance in pediatrics is so critical that extensive translational
research is warranted to improve our ability to estimate safe and efficacious doses in different pediatric populations from retrospective
clinical studies in adults.
Biotherapeutics, proteins and peptides-based drugs, generally depend on absorption (A), distribution (D), metabolism (M), and excretion
(E) in their disposition as small molecules, but the underlying mechanisms and potential drug interaction propensity can be very different.
In this article, the factors that alter pediatric and adult PK parameters are compared, and pediatric and adult PK parameters and potential
drug interactions for selected biotherapeutics are summarized. Moreover, challenges of studying therapeutic proteins and peptides in pediatrics
Keywords: Biotherapeutics, drug disposition, small molecules, ADME, monoclonal antibodies, pediatric populations, pharmacokinetics, drug clearance, DDI, Disposition, Interaction, Pediatric, PK parameters, clinical studies, dosing regimens, metabolism, ADME, monoclonal antibodies.
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