**3. Drug pharmacokinetics**

The term *pharmacokinetics refers to the way a drug is handled by the body. Pharmacokinetic*  measures, such as area under the curve (AUC) and concentration at the maximum (Cmax) and parameters calculated from those measures, such as clearance, half-life, and volume of distribution, reflect the absorption (A), distribution (D), and elimination (E) of a drug from the body. A drug can be eliminated by both metabolism (M) to one or more active and inactive metabolites and excretion of the unchanged drug. The overall set of processes is often referred to as ADME, which ultimately controls systemic exposure to a drug and its metabolites after drug administration (Buxton & Benet, 2011).

This systemic exposure, reflected in plasma drug and/or metabolite concentrations, is generally used to relate dose to both beneficial and adverse effects. All drugs show interand intra-individual variance in pharmacokinetic measures and/or parameters (Buxton & Benet, 2011). Variances can sometimes be substantial. In the pediatric population, growth and developmental changes in factors influencing ADME also lead to changes in pharmacokinetic measures and/or parameters. To achieve AUC and Cmax values in children similar to values associated with effectiveness and safety in adults, it may be important to evaluate the pharmacokinetics of a drug over the entire pediatric age range in which the drug will be used. Where growth and development are rapid, adjustment in dose within a single patient over time may be important to maintain a stable systemic exposure.

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, and gastrointestinal enzyme systems for drugs that are actively transported across the gastrointestinal mucosa, gastrointestinal permeability, and biliary function.
