Abstract
Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point. This review summarizes the comparative postnatal development of pigs and humans and discusses the advantages of the juvenile pig in view of developmental pharmacology, pediatric diseases, drug discovery and drug safety testing. Furthermore, limitations and unexplored aspects of this large animal model are covered. At this point in time, the potential of the neonatal and juvenile pig as nonclinical safety models for pediatric drug development is underexplored.
Highlights
Clinical pharmacology aims to evaluate and understand drug-specific-effects based on pharmacokinetics (PK) and pharmacodynamics (PD)
Throughout pediatric life, it is reasonable to anticipate that both PK as well as PD are affected by developmental changes, reflecting both maturation and growth or weight/size changes [1]
One of the main reasons for this is the fact that pediatric regulatory guidelines recommend using the same species and strain in juvenile animal studies as in adult repeated dose toxicity studies
Summary
Clinical pharmacology aims to evaluate and understand drug-specific (side)-effects based on pharmacokinetics (PK) and pharmacodynamics (PD). These PK profiles are further affected by a diverse set of nonmaturational covariates, including but not limited to genetics, disease characteristics (e.g., obesity, chronic inflammation, critical illness, chronic kidney disease, asphyxia) or environmental factors (e.g., type of nutrition, comedication, drug formulation, treatment modalities like therapeutic hypothermia) [12] In pediatric pharmacotherapy, it should not be taken for granted that a given level of drug exposure to adults will result in similar drug effects in children, as concentrationeffect profiles may display developmental PD [13]. At the other end of the spectrum, with diseases that are unique to a given subpopulation within pediatrics, pig models can be instrumental in drug discovery and development for accurate mechanistic understanding of the disease or condition Specific to neonates, this has been described for, e.g., necrotizing enterocolitis (NEC), resuscitation practices, or asphyxia.
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