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MODULE 4: PHARMACOKINETICS

LEARNING OBJECTIVES
After reading this module (4), the student should be able to:
1. Explain the applications of pharmacokinetics to clinical practice.
2. Identify the four components of pharmacokinetics.
3. Explain how substances travel across plasma membranes.
4. Discuss factors affecting drug absorption.
5. Explain the metabolism of drugs and its applications to pharmacotherapy.
6. Discuss how drugs are distributed throughout the body.
7. Describe how plasma proteins affect drug distribution.
8. Identify major processes by which drugs are excreted.
9. Explain how enterohepatic recirculation might affect drug activity.
10. Explain the applications of a drug’s onset, peak, and plasma half-life (t½) to duration
of pharmacotherapy.
11. Explain how a drug reaches and maintains its therapeutic range in the plasma.
12. Differentiate between loading and maintenance doses

1. Pharmacokinetics: How the Body Handles Medications

 The term pharmacokinetics is derived from the root words pharmaco, which means
“medicine,” and kinetics, which means “movement or motion.”
› Pharmacokinetics is thus the study of drug movement throughout the body. In
practical terms, it describes how the body deals with medications.

 The many processes of pharmacokinetics are grouped into four categories: absorption,
distribution, metabolism, and excretion

2. The Passage of Drugs through Plasma Membranes

 Pharmacokinetic variables depend on the ability of a drug to cross plasma membranes.
› With few exceptions, drugs must penetrate these membranes to produce their
effects.
› Like other chemicals, drugs primarily use two processes to cross body
membranes:
1. Active transport. This is movement of a chemical against a
concentration or electrochemical gradient; cotransport involves the
movement of two or more chemicals across the membrane.
2. Diffusion or passive transport. This is movement of a chemical from an
area of higher concentration to an area of lower concentration.

 Plasma membranes consist of a lipid bilayer, with proteins and other molecules
interspersed in the membrane. This lipophilic membrane is relatively impermeable to

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large molecules, ions, and polar molecules. These physical characteristics have direct
application to pharmacokinetics.

3. Absorption of Medications
 Absorption is a process involving the movement of a substance from its site of
administration, across body membranes, to circulating fluids.
› Drugs may be absorbed across the skin and associated mucous membranes,
or they may move across membranes that line the gastrointestinal (GI) or
respiratory tract

 Most drugs, with the exception of a few topical medications, intestinal anti-infectives, and
some radiologic contrast agents, must be absorbed to produce an effect

 Absorption is the primary pharmacokinetic factor determining the length of time it takes a
drug to produce its effect.
› In order for a drug to be absorbed it must dissolve. The rate of dissolution
determines how quickly the drug disintegrates and disperses into simpler
forms; therefore, drug formulation is an important factor of bioavailability.
› In general, the more rapid the dissolution, the faster the drug absorption and
the faster the onset of drug action.

4. Distribution of Medications

 Distribution involves the transport of drugs throughout the body.

› The simplest factor determining distribution is the amount of blood flow to body
tissues.
› The heart, liver, kidneys, and brain receive the most blood supply. Skin, bone,
and adipose tissue receive a lower blood supply; therefore, it is more difficult
to deliver high concentrations of drugs to these areas.

 The physical properties of the drug greatly influence how it moves throughout the body
after administration.
› Lipid solubility is an important characteristic, because it determines how quickly
a drug is absorbed, mixes within the bloodstream, crosses membranes, and
becomes localized in body tissues.
› Lipid-soluble agents are not limited by the barriers that normally stop water-
soluble drugs; thus, they are more completely distributed to body tissues.

5, Metabolism of Medications
 Metabolism, also called biotransformation, is the process of chemically converting a drug
to a form that is usually more easily removed from the body.
› Metabolism involves complex biochemical pathways and reactions that alter
drugs, nutrients, vitamins, and minerals.
› The liver is the primary site of drug metabolism, although the kidneys and cells

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of the intestinal tract also have high metabolic rates

 During metabolism, the addition of side chains, known as conjugates, makes drugs more
water soluble and more easily excreted by the kidneys.

6. Excretion of Medications
 Drugs are removed from the body by the process of excretion.
› The rate at which medications are excreted determines the concentration of the
drugs in the bloodstream and tissues.
. This is important because the concentration of drugs in the
bloodstream determines their duration of action.
› Pathologic states, such as liver disease or renal failure, often increase the
duration of drug action in the body because they interfere with natural
excretion mechanisms.

 Although drugs are eliminated from the body by numerous organs and tissues, the
primary site of excretion is the kidney

 There are many factors that can affect drug excretion. These include the following:
. Liver or kidney impairment.
. Blood flow.
. Degree of ionization.
. Lipid solubility.
. Drug–protein complexes.
. Metabolic activity.
. Acidity or alkalinity (pH).
. Respiratory, glandular or biliary activity.

7. Drug Plasma Concentration and Therapeutic Response

 The therapeutic response of most drugs is directly related to their level in the plasma.
Although the concentration of the medication at its target tissue is more predictive of
drug action, this quantity is impossible to measure in most cases.

 Minimum effective concentration is the amount of drug required to produce a therapeutic

effect. Toxic concentration is the level of drug that will result in serious adverse effects.
The plasma drug concentration between the minimum effective concentration and the
toxic concentration is called the therapeutic range of the drug.

 For each drug administered, the nurse’s goal is to keep its plasma concentration in the
therapeutic range. For some drugs, the therapeutic range is quite wide; for other
medications, the difference between a minimum effective dose and a toxic dose may be
dangerously narrow.

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8. Onset, Peak Levels and Duration of Drug Action

 Onset of drug action represents the amount of time it takes to produce a therapeutic
effect after drug administration.
› The peak plasma level occurs when the medication has reached its highest
concentration in the bloodstream. It should be mentioned that depending on
accessibility of medications to their targets, peak drug levels are not
necessarily associated with optimal therapeutic effect. In addition, multiple
doses of medication may be necessary to reach therapeutic drug levels.

 Duration of drug action is the amount of time it takes for a drug to maintain its desired
effect until termination of action.

 The most common description of a drug’s duration of action is its plasma half-life (t½),
defined as the length of time required for the plasma concentration of a medication to
decrease by one-half after administration.
› The longer it takes a medication to be excreted, the greater the half-life. For
example, a drug with a t½ of 10 hours would take longer to be excreted and
thus produce a longer effect in the body than a drug with a t½ of 5 hours
› If a patient has extensive renal or hepatic disease, the plasma half-life of a
drug will increase, and the drug concentration may reach toxic levels. In these
patients, medications must be given less frequently, or the dosages must be
reduced.

9. Loading doses and Maintenance Doses

 A loading dose is a higher amount of drug, often given only once or twice to “prime” the
bloodstream with a sufficient level of drug. Before plasma levels can drop back toward
zero, intermittent maintenance doses are given to keep the plasma drug concentration in
the therapeutic range

 Loading doses are particularly important for drugs with prolonged half-lives and for
situations in which it is critical to raise drug plasma levels quickly, as might be the case
when administering an antibiotic for a severe infection.

SUMMARY:
1. Pharmacokinetics focuses on the movement of drugs throughout the body after they are
administered.
2. The physiological properties of plasma membranes determine movement of drugs
throughout the body. The four components of pharmacokinetics are absorption, metabolism,
distribution, and excretion.
3. Absorption is the process by which a drug moves from the site of administration to the
bloodstream. Absorption depends on the size of the drug molecule, its lipid solubility, its
degree of ionization, and interactions with food or other medications.

4. Distribution comprises the methods by which drugs are transported throughout the body.
Distribution depends on the formation of drug–protein complexes and special barriers such

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as the placenta or brain barriers.

5. Metabolism is a process that changes a drug’s activity and makes it more likely to be
excreted. Changes in hepatic metabolism can significantly affect drug action.
6. Excretion processes eliminate drugs from the body. Drugs are primarily excreted by the
kidneys but may be excreted into bile, by the lung, or by glandular secretions.
7. The therapeutic response of most drugs depends on their concentration in the plasma. The
difference between the minimum effective concentration and the toxic concentration is called
the therapeutic range.
8. Onset, peak plasma level, and plasma half-life represent the duration of action for most
drugs.
9. Repeated dosing allows a plateau drug plasma level to be reached. Loading doses allow a
therapeutic drug level to be reached rapidly

Reference: Pharmacology for Nurses: A pathophysiologic Approach by Adams, Holland and Urban (pp.59
– 67)

Pharmacokinetics Celia Cruz-Fajardo, M.D.