Pharmacokinetics
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.
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