Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults

Abstract

Many physiologic differences between children and adults may result in age-related changes in pharmacokinetics and pharmacodynamics. Factors such as gastric pH and emptying time, intestinal transit time, immaturity of secretion and activity of bile and pancreatic fluid among other factors determine the oral bioavailability of pediatric and adult populations. Anatomical, physiological and biochemical characteristics in children also affect the bioavailability of other routes of administration.Key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein binding and total body water. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I and phase II metabolic enzymes. Immaturity of glomerular filtration, renal tubular secretion and tubular reabsorption at birth and their maturation determine the different excretion of drugs in the pediatric population compared to adults.

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

“…For example, the most important cellular components of the gastrointestinal immune system are already present in fetal life (Tourneur and Chassin, 2013), but a newborn still has immature intestinal mucosal layer, immunological and metabolic functions (Fernandez et al, 2011;Jakobsson et al, 2014;Levy and Wynn, 2014;Pichichero, 2014). After a few months, infants are able to absorb fat-soluble compounds efficiently because of maturation of bile salt (Fernandez et al, 2011). Furthermore, the full maturation and activation of immune system requires the stimulation of microbiota during many years after birth.…”

Challenges Caring for Adults With Congenital Heart Disease in Pediatric Settings: How Nurses Can Aid in the Transition

“…Children are not small adults, and differences in their physiology lead to changes in pharmacokinetics and pharmacodynamics. 17 Factors including variations in gastric pH, gastric emptying, protein binding, immaturity of bile secretion and activity, and glomerular filtration rate require consideration when the dosage of medications is being determined. 17 Many more medications for adults have been approved by the US Food and Drug Administration, whereas pediatric patients use off-label recommendations adapted from adult studies, owing to the smaller populations of child patients and the limited testing in children.…”

“…17 Factors including variations in gastric pH, gastric emptying, protein binding, immaturity of bile secretion and activity, and glomerular filtration rate require consideration when the dosage of medications is being determined. 17 Many more medications for adults have been approved by the US Food and Drug Administration, whereas pediatric patients use off-label recommendations adapted from adult studies, owing to the smaller populations of child patients and the limited testing in children. 18 For example, anticoagulation medications used in children often include heparin, enoxaparin, and warfarin, whereas drugs such as dabigatran and rivaroxaban are newer options used in adults that do not require frequent monitoring or dose adjustments.…”

Shared decision making in primary care: barriers and facilitators of shared decision making in the context of decreasing the use of unnecessary antibiotics for preschool children ages 3-5 with upper respiratory tract infections

“…Children younger than six years of age are more susceptible to adverse effects from antibiotics than adults, due to alterations in pharmacokinetics (Alomar, 2014;Alumran, Hou, & Hurst, 2013;Fernandez et al, 2011). Children have higher total body water and less body fat than adults, causing increased drug distribution (Fernandez et al, 2011). Immature metabolic enzymes in children may alter plasma concentrations of medications, which can increase the risk of adverse drug effects (Fernandez et al, 2011).…”

“…Children have higher total body water and less body fat than adults, causing increased drug distribution (Fernandez et al, 2011). Immature metabolic enzymes in children may alter plasma concentrations of medications, which can increase the risk of adverse drug effects (Fernandez et al, 2011). Common adverse effects from antibiotics include diarrhea, rash, and abdominal pain (Hersh et al, 2013).…”