During the neonatal period, there is physiological immaturity of organs, systems and metabolic pathways that influences the pharmacokinetics and pharmacodynamics of administered drugs, the dosage of which should be constantly amended, considering the progressive increase in weight and the maturation of the elimination pathways.

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. 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.

Intravenous (IV) drug therapy is usually recommended if not essential for the sick neonate owing to the unreliable and unpredictable gastrointestinal drug absorption. Some of the more common problems of parenteral infusion are related to the infusion rates of neonatal IV fluids. When retrograde infusion is used Y-injection ports may trap small volumes of drug. In-line filters absorb certain drugs. Drugs may be diluted within the reservoir volume; they may infuse more slowly or become trapped at the bottom of the reservoir if they are much heavier than the IV solution. The hub of a syringe contains about 0.1 ml and if IV fluid or blood from a catheter is drawn back into the syringe after infusion of a small volume dose, a potentially large extra amount of drug may be administered.

IM drug therapy may be used in larger, well-perfused infants. The rate of absorption of drug from IM administration depends on the blood flow to the site. IM administration is not appropriate if the infant is cold or vasoconstricted. IM administration of a high dose of a drug that is caustic and burns tissue may produce a depot effect in which the drug remains in a puddle-like collection within the tissue and absorption is delayed and often incomplete. Sterile abscesses may develop from IM administration in small neonates with limited muscle mass.

The goal of drug therapy is to produce an effective concentration of free or unbound drug at a specific site to achieve the therapeutic effect. Many drugs both acidic and basic are bound to various serum and tissue proteins. Albumin binds primarily to acidic drugs, whereas basic drugs are usually bound to other plasma proteins. Only free, unbound drug is active and available to interact with tissue receptors and produce the therapeutic effect as well as to be metabolized and excreted. Drugs that are more than 90% bound to protein are considered highly protein-bound. Therapeutic monitoring of plasma or serum drug concentrations usually measure total drug concentration, including bound and free drug. Displacement of highly protein-bound drug from its binding sited does not change the total drug concentration initially, but increases the amount of active drug interacting with tissue receptors, which increases the drug effects and increased metabolism or excretion.

Regards
Rutherford
Managing Editor
Journal of pharmacy Practice and Education