Back to Basics: Understanding Drugs in Children: Pharmacokinetic Maturation

1. Maria Tetelbaum, MD* 2. Yaron Finkelstein, MD* 3. Alejandro A. Nava-Ocampo, MD* 4. Gideon Koren, MD* 1. *Division of Clinical Pharmacology & Toxicology, Department of Pediatrics and Population Health Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada After completing this article, readers should be able to: 1. Recognize age-related changes in pharmacokinetics and pharmacodynamics of drugs. 2. Describe the dynamics of rational drug dosing for neonates and children. 3. Identify areas of challenge where more drug research is needed during development. Rapid age-related physiologic changes in the pediatric age group, especially during the first postnatal year, affect the absorption, distribution, metabolism, and elimination of drugs. This article reviews pharmacokinetic principles in neonates, infants, and children to help pediatricians understand the rationale for drug therapy and toxicity in these patients. Drugs are administered through a wide range of routes (Table 1). General pharmacokinetic and pharmacodynamic principles can be defined by grouping them in two major routes: intravascular and extravascular. Extravascular administration entails absorption, distribution, metabolism, and excretion. Bioavailability is the fraction of drug reaching the systemic circulation following its administration by any route. Because drugs administrated intravenously do not require an absorption process, their bioavailability is 100%. | Intravascular | || | Extravascular | |     Less Common: | Table 1. Primary Routes of Drug Absorption in Children ### Oral Administration Among the extravascular routes, oral administration commonly is used not only because it is painless, but also because technology involved in oral formulations is relatively less costly and requires fewer pharmaceutical processes. However, in some cases, the choice of administration route depends on the site of action, the desired plasma drug concentrations, and the time at which a certain drug concentration must be achieved. Bioavailability after oral administration naturally is less than after intravenous administration. The primary factors affecting oral bioavailability are listed in Table 2. | Physicochemical Factors | || | Physiologic Factors |

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