Pharmacokinetics defines the relationship between the dose of a drug and its concentration in different parts of the body (usually plasma) in relation to time. This relationship is measured and defined numerically. Knowledge of several key terms is needed to understand pharmacokinetic principles.
• Absorption: if a drug is given IV, 100% of the dose enters the blood stream. If a drug is given orally, usually only a fraction is absorbed and the term bioavailability is used to describe the percentage of the drug administered that reaches the systemic circulation. Absorption is often reduced following oral administration in the neonatal period.
• Volume of distribution (V): this is not a physiological volume but rather an apparent volume into which the drug would have to distribute to achieve the measured concentration. Water-soluble drugs, such as gentamicin, have a V that is similar to the extracellular fluid volume. Drugs that are highly bound to plasma proteins have a low V. Children differ from adults because of their body composition (neonates and young children have a higher proportion of body water) and lower plasma protein concentrations.
• Clearance: describes the removal of a drug from the body and is defined as the volume (usually of plasma) that is completely cleared of drug in a given time. In adults, clearance is described in relation to volume/time (mL/min). In children, clearance is also described in relation to body weight (mL/min/kg). Clearance is usually reduced in the neonatal period but may actually be higher in infants and young children than in adults.
• Elimination half-life: this is the time taken for the concentration of a drug (usually plasma) to fall to half the original value. It is inversely related to clearance. Therefore, 50% of the dose will be eliminated in 1 half-life; 97% of a drug will be eliminated after 5 half-lives. This is also the time required for steady state to be achieved following initial administration of the drug.
Mathematical formulae are available in standard texts that describe the interrelationship between clearance, volume of distribution, and elimina-tion half-life.