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Clinical pharmacokinetics is the discipline that applies pharmacokinetic
concepts and principles in humans in order to design individualized
dosage regimens which optimize the therapeutic response of a medication
while minimizing the chance of an adverse drug reaction. Pharmacokinetics
is the study of the absorption, distribution, metabolism, and excretion of drugs.1 When
drugs are given extravascularly (e.g., orally, intramuscularly,
applied to the skin via a transdermal patch, etc.), absorption must take place for the
drug molecules to reach the systemic circulation. In order to be
absorbed, the drug molecules must pass through several physiological
barriers before reaching the vascular system. For example, when
a medication is given orally, the drug dosage form must release
drug molecules via dissolution, and the molecules must pass through
the various layers of the gastrointestinal tract where they enter
capillaries. Distribution occurs when
drug molecules that have entered the vascular system pass from the
bloodstream into various tissues and organs such as the muscle or
heart. Metabolism is the chemical conversion
of the drug molecule, usually by an enzymatically mediated reaction,
into another chemical entity referred to as a metabolite. The
metabolite may have the same, or different, pharmacological effect
as the parent drug, or even cause toxic side effects. Excretion is the irreversible removal
of drug from the body and commonly occurs via the kidney or biliary
tract.
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Pharmacodynamics is the relationship
between drug concentration and pharmacological response. It is extremely
important for clinicians to realize that the change in drug effect
is usually not proportional to the change in drug dose or concentration
(Figure 1-1). For example, when a drug dose or concentration is
increased from a baseline value, the increase in pharmacological
effect is greater when the initial dose or concentration is low
compared to the change in drug effect observed when the initial
dose or concentration is high. Thus, the increase in pharmacological
effect that one observes in a patient as the dose is increased is
subject to the law of diminishing returns and will eventually reach
a maximum. The reason that most drugs follow this pattern is because
their pharmacological effect is produced by forming a complex with
a drug receptor. Once the drug-receptor complex is formed, the pharmacological
effect is expressed. Often, toxic side effects of drugs follow the
same type of dose- or concentration-response relationship, albeit
shifted to the right on the dose or concentration axis. In clinical
situations, patients may need to tolerate some side effects in order
to obtain the maximal pharmacological effect of the agent.
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