Basics and Dynamics of Neonatal and Pediatric Pharmacology

Abstract

Understanding the role of ontogeny in the disposition and actions of medicines is the most fundamental prerequisite for safe and effective pharmacotherapeutics in the pediatric population. The maturational process represents a continuum of growth, differentiation, and development, which extends from the very small preterm newborn infant through childhood, adolescence, and to young adulthood. Developmental changes in physiology and, consequently, in pharmacology influence the efficacy, toxicity, and dosing regimen of medicines. Relevant periods of development are characterized by changes in body composition and proportion, developmental changes of physiology with pathophysiology, exposure to unique safety hazards, changes in drug disposition by major organs of metabolism and elimination, ontogeny of drug targets (e.g., enzymes, transporters, receptors, and channels), and environmental influences. These developmental components that result in critical windows of development of immature organ systems that may lead to permanent effects later in life interact in a complex, nonlinear fashion. The ontogeny of these physiologic processes provides the key to understanding the added dimension of development that defines the essential differences between children and adults. A basic understanding of the developmental dynamics in pediatric pharmacology is also essential to delineating the future directions and priority areas of pediatric drug research and development.

What Should We Do about Low Blood Pressure in Preterm Infants

“…Increased syringe size will result in increased bolus volume caused by vertical displacement. Clinicians need to be aware of flow variability, which has been highlighted in a number of animal studies [47,48,49,50]. …”

Recommended strategies for the oral administration of paediatric medicines with food and drinks in the context of their biopharmaceutical properties: a review

“…Traditional homeopathic or herbal medicines are preferred in some societies instead of western medicines that are viewed as 'too strong' or with 'too many' side effects. [33] Traditional beliefs, misconceptions and irrational use of medicines, may be more pronounced in resource-poor settings (education) and where other services are limited (i.e. access to clean water).…”

Dosing in neonates: special considerations in physiology and trial design

“…Higher concentrations of drug in the brain are more likely in neonates than in children and adults due to decreased protein binding, a higher relative brain weight, and higher ratio of cerebral to systemic blood flow (24). …”

“…Rates of hepatic drug metabolism generally correspond with the expression of these enzymes, which is typically low at birth and gradually increases over time (2, 13, 15, 24, 30–33). Neonates are often exposed to drugs affected by enzymes with these changes in expression (Table 1).…”