Neonatal Pharmacology and Pharmacokinetics

After completing this article, readers should be able to: 1. Summarize the impact of gestational age, postnatal age, and disease state on drug absorption, distribution, metabolism, and elimination. 2. Describe first-order, one-compartment pharmacokinetics and calculate kinetic parameters. 3. Describe zero-order or saturation kinetics. 4. Characterize common pharmacodynamic models. There are important differences among the preterm neonate, term neonate, and young infant in terms of drug disposition (absorption, distribution, metabolism, and elimination). Variables such as gestational age, body composition, postnatal age, concomitant drug therapy, acidemia/hypoxemia, and end-organ perfusion may affect and complicate drug therapy. Additionally, developmental issues pertain to drug-receptor interactions, receptor number, receptor affinity, and receptor regulation and modulation. The neonate is in a rapid and continuous state of maturation, which can influence significantly the therapeutic and toxic effects of drug therapy. Our understanding of the age- and disease-related differences in the preterm neonate continues to advance through detailed clinical pharmacokinetic and pharmacodynamic evaluations. The purpose of this article is to: 1) explore the differences in drug disposition for the preterm infant and consider how these differences affect drug therapy regimens, 2) review common pharmacokinetic principles as they relate to clinical therapeutic drug monitoring, and 3) examine common pharmacodynamic models. ### Drug Absorption Absorption, the first of four major steps involved with drug disposition, refers to the translocation of drug from the site of administration into the systemic circulation. Drugs administered intravascularly (intravenous or intra-arterial) have rapid and complete bioavailability. Drugs administered extravascularly (oral, rectal, inhalation, topical, intramuscular) must cross multiple membranes to reach the target site of action. This translocation process can be affected by a variety of age-dependent factors. The primary mechanism of drug absorption is passive diffusion of neutral (unionized) molecules through lipophilic membranes into the systemic circulation. Therefore, the environmental pH at the site of absorption is important. For orally administered drugs, bioavailability …