Pharmacokinetic measures, such as area under the curve and maximum concentration (Cmax) and parameters such as clearance, half-life, and volume of distribution, reflect the  absorption, distribution, and excretion  of a drug or biologic from the body. Drugs may be eliminated in the unchanged (parent) form, or undergo metabolism to one or more active and inactive metabolites. The overall set of processes is often referred to as ADME, which ultimately determines systemic exposure to a drug and its metabolites after drug administration. This systemic exposure, reflected in plasma drug or metabolite concentrations, or both, is generally correlated with both beneficial and adverse drug effects. All drugs and biologics show inter- and intra-individual variability in PK measures and parameters. In the pediatric population, growth and developmental changes in factors influencing ADME can also lead to changes in PK parameters. The PK of a drug or biologic is typically evaluated over the entire pediatric age range in which the agents will be used. Special areas of importance in planning pediatric PK studies are discussed in the following paragraphs.

 Developmental changes in the pediatric population that can affect absorption include effects on gastric acidity, rates of gastric and intestinal emptying, surface area of the absorption site, gastrointestinal drug-metabolizing enzyme systems, gastrointestinal permeability, biliary function, and transporter expression. Similarly, developmental changes in skin, muscle, and fat, including changes in water content and degree of vascularization, can affect absorption patterns of drugs delivered by intramuscular, subcutaneous, or percutaneous absorption Distribution of a drug or biologic can be affected by changes in body composition, such as changes in total body water and adipose tissue, which are not necessarily proportional to changes in total body weight. Plasma protein binding and tissue binding changes arising from changes in body composition with growth and development may also influence distribution. Differences between pediatric patients and adults in blood flow to an organ, such as the brain, can also affect the distribution of a drug or biologic in the body.

 Drug metabolism commonly occurs in the liver, but may also occur in the blood gastrointestinal wall, kidney, lung, and skin. Developmental changes in metabolizing capacity can affect both bioavailability and elimination, depending on the degree to which intestinal and 168 hepatic metabolic processes are involved. Although developmental changes are recognized, information on drug metabolism of specific drugs in newborns, infants, and children is limited. Both rates of metabolite formation and the principal metabolic pathway can be different in pediatric patients compared to adults and within the pediatric population. In vitro studies performed early in drug development may be useful in focusing attention on Drug excretion by the kidney is the net result of glomerular filtration, tubular secretion, and tubular reabsorption. Because these processes mature at different rates in the pediatric population, age can affect the systemic exposure of drugs when renal excretion is a dominant pathway of elimination. The maturation of other excretory pathways, including biliary and pulmonary routes of excretion, is also important.

Best Regards,
Nancy Ella
Associate Managing Editor
Drug Designing: Open Access