Pharmacokinetics – Drugs and Behavior (2023)

For the past three chapters, we have looked at the human nervous system from the overall structure down to the individual synapse. For the next two chapters, we will be bringing drugs to the forefront by exploring pharmacology, which can be divided into two main branches. The first branch—pharmacokinetics—is the focus of this chapter.

Just like with neuroscience, pharmacology is a vast and complex subject that is often studied over multiple semesters. This discussion will be simplified somewhat, but there will still be many new terms and concepts to learn. Nevertheless, doing so will be vital, as these ideas will show up again and again when we transition to looking at specific types of drugs for the rest of the semester. Stay focused, and be sure to reach out to your instructor if you need help.

Chapter Outline:

5.1 Overview of Pharmacology

  • 5.1.1 The Pharmaceutical Sciences
  • 5.1.2 ADME

5.2 Absorption

  • 5.2.1 Determinants of Absorption
  • 5.2.2 Enteral Routes
  • 5.2.3 Parenteral Injection Routes
  • 5.2.4 Parenteral Non-Injection Routes

5.3 Distribution

  • 5.3.1 Plasma Protein Binding
  • 5.3.2 The Blood-Brain Barrier

5.4 Metabolism

  • 5.4.1 Metabolism in the Liver
  • 5.4.2 Enzyme Induction and Inhibition
  • 5.4.3 Prodrugs

5.5 Excretion

  • 5.5.1 Routes of Excretion
  • 5.5.2 Elimination Kinetics

5.1 Overview of Pharmacology

As mentioned in the introduction, this chapter is the start of our exploration of pharmacology, which is the study of the actions and effects of drugs. You can easily see how such a field is relevant to a class with the words “effects of alcohol and other drugs” in its name. Pharmacology is the foundation of many health sciences and is critical to developing therapeutic drugs and drug treatments.

By the end of this section, you should be able to:

  • Differentiate between pharmaceutics, pharmacokinetics, and pharmacodynamics.
  • Define the four different components of pharmacokinetics.

5.1.1 The Pharmaceutical Sciences

Pharmacology can be broken down into two different branches: pharmacokinetics, which is the study of how the drug moves around the body, and pharmacodynamics, which is the study of how the drug changes the body. You can use these meanings to tell the two terms apart; the suffixes ‑kinetics [movement] and ‑dynamics [change] refer to how the drug moves and what the drug changes.

Pharmacology is only one of many different areas of study related to drugs. Another example is medicinal chemistry, which is the synthesis of new drug compounds. We briefly touched on it during the discussion of the New Drug Approval process in the first chapter, although not by name. There are other fields as well, each with many different subspecialties.

One area worth mentioning is pharmaceutics, or the study of how a drug is formulated and dispensed. In the past, pharmacists often dispensed drugs directly as a powder containing just the active ingredients. Nowadays, drugs are usually designed with a dosage form in mind, which is a mix of active and inactive ingredients prepared in a particular form, such as a capsule or tablet. Dosage forms allow for greater control over the dose of the drug and how it is taken.

Although we will not cover pharmaceutics in detail in this course, it is worth knowing because of the relationship between pharmaceutics and pharmacokinetics. As you can see in the diagram below, the dosage form determines how the drug is made available to the body. This influences the pharmacokinetics of the drug, which in turn influences the pharmacodynamics of the drug.

Pharmacokinetics – Drugs and Behavior (1)

5.1.2 ADME

The focus of this chapter is pharmacokinetics, which as we just mentioned is concerned with how the drug moves throughout the body. In reality, the drug isn’t moving on its own—it’s actually being moved around by the natural systems in our body. Because of this, we can also say that pharmacokinetics is what the body does to the drug. (Next chapter we will look at pharmacodynamics, which is the opposite—what the drug does to the body.)

There are four main things that the body does to the drug: it absorbs it into the bloodstream, distributes it to various areas of the body, metabolizes it into different compounds, and excretes it from the system. A useful mnemonic that can help you remember this process is ADMEAbsorption, Distribution, Metabolism, and Excretion. We will spend the rest of this chapter examining each of these in detail.

(Video) Lecture 3 Pharmacokinetics: Drug Metabolism Drugs and Human Behavior 2019

5.2 Absorption

The first factor that influences how a drug moves throughout the body is absorption. Absorption describes the movement of the drug from its site of administration to the circulatory system. For most drugs, the bloodstream is what will carry the drug to its site of action. As such, understanding how the drug gets absorbed into the bloodstream is an important component of pharmacokinetics.

By the end of this section, you should be able to:

  • Define bioavailability and diffusion.
  • Explain how a drug’s ability to permeate membranes is critical to absorption and describe what factors can influence this.
  • Describe different routes of administration and explain how they influence drug absorption and bioavailability.

5.2.1 Determinants of Absorption

Following administration, not all of the drug will be absorbed into the bloodstream, and not always at the same rate. The amount that does get absorbed is termed the bioavailability, expressed as a percentage of the amount administered. Some drugs will also be absorbed more quickly, which can increase the strength of their effects.

The bioavailability and rate of absorption depend heavily on how well the drug can diffuse from its site of administration. Diffusion simply refers to a substance spreading out, i.e., moving from an area of high concentration to low concentration. We have already encountered this idea before when discussing action potentials in chapter 3. A drug that can easily pass through membranes will diffuse faster than one that cannot.

How well the drug can permeate these membranes depends on certain properties of the drug. Larger molecules, ionized chemicals, and hydrophilic (water-loving) substances all have a harder time passing through membranes. This is because the phospholipid bilayers that make up cell membranes consist of hydrophilic heads and uncharged tails that repel hydrophilic and ionized molecules.

Aside from diffusion that occurs on its own, known as passive diffusion, drugs can also be moved via active transport mechanisms. These mechanisms, such as ion channels and transport proteins, consume energy but can move larger molecules and work against concentration gradients. By now, you should be familiar with the ion channels found in nervous tissue; similar channels exist in different cells. Active transport can allow drugs with larger molecules to pass through membranes and be absorbed.

The rate of absorption and bioavailability also depend on the route of administration, or the path that the drug takes into the body. Some paths are more direct that others—a drug that is injected directly into the bloodstream will by definition have 100% bioavailability, while drugs that pass through the gastrointestinal tract face a gauntlet of obstacles that will slow down the rate of absorption and reduce the total amount of the drug that reaches the systemic circulation. Recall that the dosage form of a drug can determine how it is taken, so the route of administration is often influenced by the drug’s pharmaceutics. Another way of looking at it is that if a certain route is preferred, the dosage form has to be changed to match.

For the remainder of this section, we will look at various routes of administration. As we cover each one, pay close attention to how they differ in terms of absorption and bioavailability.

5.2.2 Enteral Routes

There are two main categories for routes of administration. The first type is the enteral route, which refers to the routes that pass through the gastrointestinal tract. (The word enteral is from the Greek for énteron, meaning “intestine”). This is usually accomplished through oral administration, or taking the drugs by mouth. This is the method of drug-taking that you are probably the most familiar with; capsules, tablets, and liquids like cough syrups and alcohol are all taken orally (although we say we drink alcohol rather than “orally administer” it). Aside from the oral route, there is also rectal administration, which involves inserting the drug directly into the rectum, as in the case of suppositories.

Of these two routes, the rectal route is faster and simpler. Drugs taken orally must first pass through the stomach. The stomach typically absorbs drugs more slowly than the intestines, so it can take longer for the drug to be absorbed. If the stomach is full of food, the drug will spend more time in the stomach, reducing the rate of absorption even further. Finally, the dosage form of oral medication is important, because not all drugs can survive the highly acidic environment in the stomach. These drugs must be enclosed in acid-resistant capsules that delay the release of the drug until after it reaches the intestine.

Both oral and rectal routes pass through the intestinal walls, which are comprised of epithelial cells. Drugs must be able to permeate these cells in order to be absorbed; otherwise, they will simply pass through the intestines and be excreted without accomplishing anything. If a drug cannot be absorbed through the intestinal wall, it may require a different route altogether.

Even if a drug makes it past the intestinal walls and into the bloodstream, it will be taken to the liver before circulating to the rest of the body. This is significant because the liver often metabolizes drugs, which may reduce the bioavailability further. We will cover this in detail when we reach the section on metabolism. For now, it is enough to grasp that enteral routes tend to have low bioavailability and slow rates of absorption, especially in the case of oral administration. In spite of this, taking medication by mouth is generally the most convenient option, so the effort to design a drug that can be taken orally—and make it all the way to the bloodstream—is usually worth it.

5.2.3 Parenteral Injection Routes

The alternative to the enteral routes is the parenteral route, which includes all the routes that do not pass through the gastrointestinal tract. This often involves an injection of some sort, although there are non-injection routes as well. We’ll start by looking at the routes that involve injection first.

First is intravenous, or IV, which involves injecting the drug into a vein. Because the drug is injected directly into the bloodstream, IV administration is fast and results in 100% bioavailability. For drugs like heroin this manifests as an immediate rush of pleasure, which is why they are often injected this way. IV therapy is also ideal for emergency use in hospitals, as it can be used for blood transfusions, fluid replacement, nutrition, and medications. The downside of the IV route is that it requires skill and knowledge to use, since a vein must be found and pierced with a needle. Although some users of drugs like heroin become proficient at IV injections, veins can collapse if they are used excessively.

Another common method of injection is intramuscular, abbreviated IM. As the name suggests, intramuscular medications are injected into the skeletal muscle, where they are absorbed into the bloodstream. The IM route results in high bioavailability but is somewhat slower than IV. Although many drugs can be administered intramuscularly, most people have experienced IM administration when getting vaccinated, as vaccines are typically given with an IM injection.

Aside from injecting the drug into the veins or muscles, it can also be injected below the skin, known as subcutaneous (sometimes abbreviated as SC or SQ). Compared to the IM or IV routes, absorption takes longer because there are fewer blood vessels underneath the skin. In exchange, subcutaneous injections are good for drugs that need to be absorbed for a long period of time, which is why insulin is usually administered subcutaneously.

(Video) Pharmacokinetics: How Drugs Move Through the Body

Another method is intraosseous infusion (IO), which involves injecting directly into bone marrow. As you may recall from biology, the marrow is the part of the bone that is responsible for producing new blood cells, and, as such, has direct access to the bloodstream. In fact, IO administration is comparable to IV in terms of speed of absorption and bioavailability. IO is useful when IV access cannot be established quickly, such as with trauma patients or during cardiac arrests; in these cases, the IO route can be used to administer fluids and drugs used in resuscitation like epinephrine.

The last injection route we will look at is intrathecal, which means injecting into the theca, or the sheath of the spinal cord that contains the cerebrospinal fluid. This route is notable because it bypasses the blood-brain barrier, an impediment to distribution that we will cover in more detail in the next section. Certain anesthetics and chemotherapy drugs are administered this way.

5.2.4 Parenteral Non-Injection Routes

Now we will look at routes that bypass the gastrointestinal tract without the need for a needle. First up is inhalation, which involves inhaling the drug as a vapor. This produces high bioavailability like IV administration but is actually faster because the drug enters the circulatory system at the lungs, instead of at the veins where it has to be carried back to the heart before being circulated. This makes inhalation a common method for recreational drug use, as it provides an immediate effect. Although smoking is convenient, the chemical byproducts produced by it can damage the lungs. Safer methods of inhalation are found in therapeutic drugs, such as the asthma inhalers that contain corticosteroids, or the anesthetics used during general surgery.

Another method is topical, which means applied to a certain place, often a body surface. This is typically the skin, as in the case of ointments or creams, but can also refer to things like eye drops and ear drops. Topical administration does not result in systemic effects; that is, instead of being absorbed in the bloodstream and distributed to the site of action, topical medications simply work locally at their intended site of action. As a result, they have negligible bioavailability and do not have to be concerned with distribution.

In comparison, transdermal administration (meaning “through the skin”) does result in the drug reaching the systemic circulation, as the drug is gradually absorbed by capillaries in the skin. This process is very slow but is similar to subcutaneous injections in that it can support sustained absorption of the drug. You have probably heard of the nicotine patches used to help people quit smoking; these are an example of transdermal administration.

A similar method of administration is sublingual. This method, which means “beneath the tongue,” involves placing a tablet underneath the tongue, where it dissolves and is absorbed by the capillaries there. Sublingual medications can also be applied as a dissolvable strip or liquid drops. Nitroglycerin tablets, used to treat angina pectoris, are administered sublingually.

Finally, drugs can be administered through a nasal route. The nasal passage contains mucosal membranes that can absorb drugs into the capillaries, similar to sublingual or transdermal routes. Drugs can be applied as a liquid or powder, that latter of which dissolves inside the nasal passage. Examples of drugs that use this route are nasal decongestant sprays and some recreational drugs that are snorted (most notably cocaine).

Before moving on, take a moment to look over the table summarizing each of the routes of administration below.

Pharmacokinetics – Drugs and Behavior (2)

5.3 Distribution

Once the drug enters the circulatory system, the bloodstream carries it to the site of action. This process is known as distribution. Distribution determines how much of the drug actually reaches the site of action, similar to how absorption determines how much enters the bloodstream in the first place. In this section, we will examine two factors that influence drug distribution: plasma protein binding and the blood-brain barrier.

By the end of this section, you should be able to:

  • Explain plasma protein binding and how it affects drug distribution.
  • Describe the blood-brain barrier and explain how it affects drug distribution.

5.3.1 Plasma Protein Binding

Not all of the drug that is absorbed will be free to activate receptors at the target area. Some amount of drug may be retained in the blood, unable to diffuse out of the circulatory system to the site of action. This is because the plasma in our blood contains many different proteins, some of which can reversibly bind to drugs in a process known as plasma protein binding. To see how it works and why it can complicate drug dosage, watch this video:

Protein Binding [5:22]

Let’s review the information covered in the video. The drug-binding plasma proteins act like sponges, “soaking” up the drug by binding to it. Once bound to the protein, the drug will be stuck inside the circulatory system and unable to reach the site of action. In order to activate receptors, it is necessary to first saturate the protein binding sites in the blood, meaning a larger amount of drug is required. The amount depends on how well the drug binds to the proteins. A drug that has a binding rate of 99% means that only 1% of the drug will be able to activate receptors, so the amount that needs to be absorbed is 100x that amount.

What complicates this process is that other drugs may also compete for these binding sites. If a new drug is introduced that binds to the same sites, it will displace some of the original drug, increasing the amount that reaches the target area. The magnitude of the change depends on each drug’s ability to bind to the plasma proteins. If a drug has a high binding rate (like in the 99% example above), even a small change in the amount of available binding sites can double or triple the amount of drug that reaches the site of action, which can result in severe effects. The opposite is also true: discontinuing a drug can render another drug ineffective, as seen in the example provided in the video. This is why it is dangerous to drink alcohol with some medications and why physicians need to be aware of what medications you’re taking before prescribing a new one.

5.3.2 The Blood-Brain Barrier

Due to how important our brain is, our body has an extra layer of security meant to protect it from pathogens and toxins that may be carried in the blood. This defense is called the blood-brain barrier (sometimes abbreviated BBB), and it is an additional boundary that separates the circulatory system from the brain. Watch this video from 2-Minute Neuroscience that explains what it is and how it works:

(Video) Pharmacology | Pharmacokinetics | INBDE, NBDE Part II

2-Minute Neuroscience: Blood-Brain Barrier [1:58]

As mentioned in the video, the blood-brain barrier is formed by tight junctions of endothelial cells, which are the cells that line blood vessels. Unlike in most parts of the body, where there are gaps between the cells to let substances through, the tight junctions in the blood-brain barrier limit which substances can diffuse through the capillaries. These tight junctions are formed with the help of astrocytes, which are a type of glial cell found in the brain (recall from chapter 3 how glial cells are the support cells of the nervous system).

The blood-brain barrier helps maintain a constant environment for the brain and protects it from foreign substances or neurotransmitters from other parts of the body. As a consequence, not all drugs can pass through the barrier. Recall the discussion of a drug’s ability to permeate membranes in the previous section; large, ionized, or hydrophilic drugs will find it harder to reach the brain. This means that if a drug’s intended site of action is in the brain, it needs to find some way of penetrating the blood-brain barrier, such as by being lipid-soluble or relying on active transport mechanisms.

Similar barriers exist in other parts of the body. The cerebrospinal fluid is protected by a barrier that lets in some substances that are blocked by the blood-brain barrier. The placental barrier also exists between a fetus and its mother, although this barrier is much more permeable to drugs and other substances, which is why expecting mothers are advised to abstain from drinking, smoking, or other drug use as the drugs can cross the barrier and harm the fetus.

5.4 Metabolism

The human body is not limited to simply moving drugs around. After all, many substances that we consume, intentionally or not, can be toxic to us. Our bodies chemically modify these substances in a process known as metabolism or biotransformation. Metabolism can transform inert substances into nutrients or alter toxic chemicals so that they are more easily expelled from the body.

When a drug is metabolized by our body, the result is called a metabolite. If a metabolite has a physiological effect of its own, it is called an active metabolite, but sometimes drugs are transformed into inactive metabolites that have no effect on the body. The transformation of a drug into active and inactive metabolites affects all other aspects of pharmacokinetics, which is why we will be taking a closer look at the process in this section.

By the end of this section, you should be able to:

  • Explain the first-pass effect and how it affects bioavailability of oral drugs.
  • Describe the metabolic processes that occur in the liver and explain the role of enzymes such as cytochrome P450.
  • Explain how enzyme inducers and inhibitors affect bioavailability.
  • Describe prodrugs and explain why they are useful.

5.4.1 Metabolism in the Liver

The main site where metabolism occurs is the liver. Although biotransformation occurs elsewhere in the body, we will focus on the liver for this course. The reason why the liver is so significant is because everything we eat and drink is sent to the liver first for processing. Substances are absorbed from the intestinal tract and carried directly to the liver by the portal vein; they are only able to reach other parts of the body after passing through the liver (see image below).

Pharmacokinetics – Drugs and Behavior (3)

What this means is that drugs absorbed from the intestinal tract are taken straight to the liver before they can be distributed to the site of action. This is known as the first-pass effect or first-pass metabolism, where some of the drug is immediately metabolized in the liver before reaching systemic circulation. This reduces the bioavailability of orally administered drugs. First-pass metabolism also affects rectal administration, but to a lesser degree as some of the drug can enter systemic circulation right away.

What exactly does metabolism entail? All metabolic processes are chemical reactions aided by enzymes, which are proteins that catalyze (speed up) the reaction. Metabolic reactions are classified into two groups: phase I and phase II. Phase I reactions typically transform the drug to make it more hydrophilic through oxidation, reduction, or hydrolysis. This is necessary because it is difficult to eliminate lipid-soluble molecules from the body, so the liver alters them to be hydrophilic or water-soluble instead. Most reactions in this phase involve enzymes called cytochrome P450.

Pharmacokinetics – Drugs and Behavior (4)

Some drugs and metabolites also undergo phase II reactions, which attach polar groups such as sulfate or glucuronic acid to the molecules in a process known as conjugation. These polar groups make the molecules even more hydrophilic, ensuring that they can be easily excreted.

5.4.2 Enzyme Induction and Inhibition

Because enzymes control the rate at which drugs metabolize, changes in enzyme activity have an impact on drug bioavailability. If the amount of an enzyme increases, the metabolism of the drug will speed up and less of the drug will be available. Drugs that increase the expression of enzymes are enzyme inducers.

Enzyme inducers can come from substances other than drugs. Saint-John’s wort, which is often used as an herbal remedy, induces the enzyme CYP3A4. This can reduce the effectiveness of drugs that are metabolized by CYP3A4, such as indinavir, an anti-HIV drug. Some drugs even induce the very enzymes that metabolize them. Phenobarbital, a barbiturate used to treat epilepsy, is one such example; over time, repeated administration will result in the drug having a reduced effect due to it being metabolized at a faster rate.

Drugs can also act as enzyme inhibitors by reducing the expression of the enzyme or blocking the enzyme’s active sites. As you might expect, this slows down metabolism of the drug, increasing its bioavailability and prolonging its effects. As with inducers, this can be done by the drug itself or by another substance. A notable example is grapefruit—the juice contains compounds that inhibit CYP3A4 enzymes, which can increase the concentrations of many medications that are metabolized by CYP3A4.

If these concepts are still confusing to you, before you move on you may want to review them by watching this short video: Enzyme Inhibition and Enzyme Induction [3:19]

(Video) Lecture 2 - Pharmacokinetics - Drug Distribution 2019

5.4.3 Prodrugs

There is one final concept worth discussing in the context of drug metabolism. So far, we have framed metabolism as a process that tends to work against the drug. Although that is the case for most drugs, not every biotransformation reduces the effectiveness of the drug. It is possible for the metabolite to be more pharmacologically active than the drug initially administered. This is the case for prodrugs: drugs that are administered in an inactive form that only becomes active after the drug is metabolized. To learn about prodrugs and examples of prodrugs, watch this brief video:

Biotransformation: Prodrugs [1:21]

Why are prodrugs useful? The chemotherapy drug mentioned in the video is a good example—sometimes the active form is too toxic to be administered directly. There are other potential reasons as well. Some prodrugs are better at crossing cell membranes. If you recall from the previous chapter, Parkinson’s disease is caused by a deficiency of dopamine. It would be nice to administer dopamine directly to treat the disease, but dopamine cannot cross the blood-brain barrier. Fortunately, its precursor, L-DOPA, is able to pass the barrier instead. This allows it to be administered as a prodrug that is converted to dopamine in the brain.

5.5 Excretion

The final step in every drug’s journey is to leave the body in some manner. Excretion is the elimination of a drug from the body, either in its unchanged form or as a metabolite. Although this may seem like an automatic process, it cannot be taken for granted. If drugs or other waste products accumulate in the body, they can cause harm, which is why energy must be constantly spent removing these substances from the body.

By the end of this section, you should be able to:

  • Describe various routes of excretion for drugs.
  • Differentiate between first-order and zero-order kinetics and define half-life.

5.5.1 Routes of Excretion

Although drugs can be excreted through a variety of routes, most drugs are excreted by the kidneys into urine. The kidneys work like filters, filtering out the waste products from the bloodstream. The exact process is complex and beyond the scope of this class, but it involves the same process of diffusion mentioned in the absorption section. Recall that lipophilic drugs need to be metabolized into hydrophilic metabolites before they can be filtered out by the kidneys, since lipid-soluble molecules would simply reenter the bloodstream. Nonionized molecules are also difficult to excrete for the same reasons. The kidneys are also unable to excrete any drug that is still bound to plasma proteins.

Because most drugs are excreted through the kidneys, drug tests usually involve taking a urine sample. By measuring the presence of a drug or its metabolites in the urine, it is possible to determine whether a drug was present in a person’s body recently. Drugs can also be excreted through the liver as bile or feces, through sweating, and even through tears, although these routes are less important when it comes to drugs. Drug tests that involve mouth swabs are testing your saliva, which is another excretory route. Another type of drug test that you have probably heard of is the breathalyzer, which measures alcohol levels in the blood just be breathing into it. This is possible because the lungs can expel certain drugs like alcohol or anesthetics from the bloodstream directly.

There is one final route that requires consideration: mother’s milk. Some drugs can be eliminated through mother’s milk, which could have adverse effects on breastfeeding infants. Although cases are rare, special caution is warranted as infants have livers and kidneys that are still developing, making them more susceptible to any toxic effects.

5.5.2 Elimination Kinetics

As a drug is eliminated from the body, the amount of drug remaining decreases over time. If we were to graph how much drug remains in the bloodstream, for most drugs we would get a shape like the graph below:

Pharmacokinetics – Drugs and Behavior (5)

This curved shape follows first-order kinetics, which means it is eliminated at a rate proportional to the amount of drug. More specifically, first-order kinetics refers to a drug being eliminated in half-lives. A half-life is the amount of time that must pass for the body to eliminate half of the drug. Take methadone, a drug used in therapy for patients with opioid addiction. In a typical patient, the half-life of methadone is approximately 24 hours (Berkowitz, 1976). If we start with 80 mg of methadone in the bloodstream, after 1 day has passed there will be 40 mg remaining. After 2 days, 20 mg; after 3 days, only 10 mg, and so on. Under first-order kinetics, the drug will be eliminated rapidly at the start, but the rate will taper off as the concentration of drug in the blood decreases.

Not all drugs follow this pattern, however. Some drugs such as alcohol are eliminated at a constant rate—the amount of drug eliminated is always the same no matter how much of the drug there is. This is known as zero-order kinetics; if we were to plot the concentration of a drug being eliminated under zero-order kinetics, it would look like the graph below:

Pharmacokinetics – Drugs and Behavior (6)

Because the drug is eliminated at a constant rate, the slope of the graph is flat instead of curved. A few drugs such as aspirin follow first-order kinetics for the most part, but once a high enough concentration of the drug is reached, the enzymes that metabolize them become saturated. When the enzymes become saturated, increased metabolism of the drug is impossible, and the elimination rate follows zero-order kinetics instead. This is rare to see in practice, however, because such levels of concentration are well above therapeutic levels.

Chapter Summary and Review

In this chapter, we explored the first branch of pharmacology, pharmacokinetics. After providing an overview of the different branches of pharmaceutical sciences, we took a journey through the four components of pharmacokinetics captured in the mnemonic ADME—absorption, distribution, metabolism, and excretion. We discussed factors that affect absorption, compared different routes of administration, learned about plasma proteins and the blood-brain barrier, examined metabolic processes, enzymes, and prodrugs, and covered the pathways and rates at which drugs can be excreted from the body. This was a dense chapter, so make sure to give yourself time to digest it, and don’t forget to check your understanding with the practice questions below.

Practice Questions

(Video) Lecture 1 - Introduction to Pharmacokinetics - Drug Administration and Absorption 2019

  • What are the different things that pharmaceutics, pharmacokinetics, and pharmacodynamics study?
  • What is the bioavailability of a drug that is administered intravenously?
  • Rank these routes of administration from fastest absorption to slowest: intramuscular injection, inhalation, and transdermal.
  • Which drug is more sensitive to competition for plasma protein binding sites: one with a high rate of binding, or one with a low rate?
  • Describe what the blood-brain barrier is made up of. How is this different from a typical blood vessel?
  • Which routes of administration are subject to the first-pass effect?
  • Does enzyme induction increase or decrease the bioavailability of a related drug?
  • What is a prodrug, and in what circumstances would it be useful?
  • Would a lipid-soluble molecule be able to be excreted by the kidneys? Explain why or why not.


1st edition


What does pharmacokinetics include with answers? ›

Pharmacokinetics is currently defined as the study of the time course of drug absorption, distribution, metabo- lism, and excretion. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient.

What is pharmacokinetic behavior? ›

Pharmacokinetics represents the absorption, distribution, metabolism, and elimination of drugs from the body. Pharmacodynamics describes the interaction of drugs with target tissues.

What is pharmacokinetics quizlet? ›

Pharmacokinetics. the study of what happens to the drug(s) in the patients body after administered. Includes absorption, distribution, metabolism and excretion.

What are the 4 steps of pharmacokinetics explain? ›

Think of pharmacokinetics as a drug's journey through the body, during which it passes through four different phases: absorption, distribution, metabolism, and excretion (ADME). The four steps are: Absorption: Describes how the drug moves from the site of administration to the site of action.

What is pharmacokinetics Mcq? ›

a) The study of biological and therapeutic effects of d–gs. b) The study of absorption, distribution, metabolism and excretion of d–gs. c) The study of mechanisms of d–g action. d) The study of methods of new d–g development. Answer: b.

What affects pharmacokinetics of a drug? ›

Pharmacokinetics can vary from person to person and it is affected by age, gender, diet, environment, body weight and pregnancy, patient's pathophysiology, genetics and drug- drug or food-drug interactions. Drug therapy is impacted by factors that affect pharmacokinetics and pharmacodynamics.

Why is it important to know the pharmacokinetics of a drug? ›

Applying pharmacokinetic principles to individual patients allows medical professionals to better understand the physical and chemical properties of drugs and how the responses correlate with the body.

What is PK study? ›

A pharmacokinetic (PK) study of a new drug involves taking several blood samples over a period of time from study participants to determine how the body handles the substance. These studies provide critical information about new drugs.

What is drug exposure in pharmacokinetics? ›

Dr. Mehrotra: Exposure refers to drug levels achieved in the body. Response can be assessed in terms of either efficacy or safety. Understanding the relationship between exposure and response is critical to finding a dose that optimally strikes a balance between drug efficacy and adverse events.

What is a pharmacodynamic drug? ›

Abstract. Pharmacodynamic drug-drug interactions (DDIs) occur when the pharmacological effect of one drug is altered by that of another drug in a combination regimen. DDIs often are classified as synergistic, additive, or antagonistic in nature, albeit these terms are frequently misused.

What is the process of metabolism in pharmacokinetics? ›

1. Pharmacokinetic processes: metabolism. Metabolism. Metabolism describes the chemical reactions that change drugs into compounds which are easier to eliminate. The products of these chemical reactions are called metabolites.

What is the process of metabolism in pharmacokinetics quizlet? ›

Metabolism gradually transforms or metabolizes the drug from its original active form to a less active, or even inactive, form. This process is accomplished in the liver, the principal organ of metabolism, by the action of liver enzymes. Also known as biotransformation.

What affects drug absorption? ›

Drug absorption depends on the lipid solubility of the drug, its formulation and the route of administration. A drug needs to be lipid soluble to penetrate membranes unless there is an active transport system or it is so small that it can pass through the aqueous channels in the membrane.

How can I learn pharmacokinetics? ›

Pharmacokinetics 1 - Introduction - YouTube

What are the four components of pharmacology? ›

There are two main branches of pharmacology: pharmacokinetics and pharmacodynamics. Pharmacokinetics is the study of what the body does to the drugs. There are four processes involved in pharmacokinetics: absorption, distribution, metabolism, and excretion.

What is first moment curve? ›

The first moment curve is prepared when concentration x time is plotted versus time. AUMC can be mathematically expressed as: (6.6) Knowledge about AUC and AUMC allows further calculation and analysis of drug characteristics.

What is drug bioavailability? ›

More accurately, bioavailability is a measure of the rate and fraction of the initial dose of a drug that successfully reaches either; the site of action or the bodily fluid domain from which the drug's intended targets have unimpeded access.[1][2][3] For majority purposes, bioavailability is defined as the fraction of ...

How is bioavailability calculated? ›

Bioavailability is calculated by comparing plasma levels of a drug given via a particular route of administration (for example, orally) with plasma drug levels achieved by IV injection. This is where the AUC comes into play (the area under the curve calculated by plotting plasma concentrations of the drug versus time).

What are the 4 factors that can affect drug distribution? ›

Drug distribution is impacted by several factors related to the drug and the body. The drug-related factors include blood and tissue binding proteins, pH, and perfusion. The body-related factors include body water composition, fat composition, diseases (e.g., volume depletion, burns, third spacing).

What is the benefits of pharmacokinetics? ›

Pharmacokinetics, along with pharmacodynamics, provides accurate data for the preclinical trial which then informs the related clinical trial. Thus, initial dosages can be accurately measured, and potential side-effects can be managed. Animal models are always used before human trials can be authorized.

What is half life of a drug? ›

The half-life of a drug is the time it takes for the amount of a drug's active substance in your body to reduce by half. This depends on how the body processes and gets rid of the drug. It can vary from a few hours to a few days, or sometimes weeks.

What is bioavailability and bioequivalence? ›

Bioequivalence is determined based on the relative bioavailability of the innovator medicine versus the generic medicine. It is measured by comparing the ratio of the pharmacokinetic variables for the innovator versus the generic medicine where equality is 1.

What is duration of action of a drug? ›

Introduction. The duration of action of a drug is known as its half life. This is the period of time required for the concentration or amount of drug in the body to be reduced by one-half. We usually consider the half life of a drug in relation to the amount of the drug in plasma.

What are the four parameters of pharmacokinetics? ›

There are four main components of pharmacokinetics: liberation, absorption, distribution, metabolism and excretion (LADME).

What parameters are used to understand the behavior of drug molecules? ›

The two main independent parameters in pharmacokinetics are drug clearance and volume of distribution; from these, the third important parameter of half-life can be determined.

What are the 3 phases of drug action? ›

A tablet or capsule taken by mouth goes through three phases—pharmaceutic, pharmacokinetic, and pharmacodynamic—as drug actions occur. In the pharmaceutic phase, the drug becomes a solution so that it can cross the biologic membrane.

What are the 3 aspects of pharmacodynamics? ›

  • Overview of Pharmacodynamics.
  • Chemical Interactions.
  • Dose-Response Relationships.
  • Drug–Receptor Interactions.

What factors affect pharmacodynamics? ›

Disorders that affect pharmacodynamic responses include genetic mutations, thyrotoxicosis, malnutrition, myasthenia gravis, Parkinson disease, and some forms of insulin-resistant diabetes mellitus.
A drug's pharmacodynamics can be affected by physiologic changes due to:
  • A disorder or disease.
  • Aging process.
  • Other drugs.

What organs are involved in pharmacokinetics? ›

[8] Different strategies of metabolism may occur in multiple areas throughout the body, such as the gastrointestinal tract, skin, plasma, kidneys, or lungs, but the majority of metabolism is through phase I (CYP450) and phase II (UGT) reactions in the liver.

What is the pharmacology of a drug? ›

Pharmacology is the science of how drugs act on biological systems and how the body responds to the drug. The study of pharmacology encompasses the sources, chemical properties, biological effects and therapeutic uses of drugs.

What is the first step in drug transport? ›

Absorption is the first step in drug transport. Distribution refers to how drugs are transported throughout the body. Metabolism is a process whereby drugs are made less or more active.

What does drug elimination mean? ›

Drug elimination is the sum of the processes of removing an administered drug from the body. In the pharmacokinetic ADME scheme (absorption, distribution, metabolism, and excretion) it is frequently considered to encompass both metabolism and excretion.

Why is solubility important in drugs? ›

Solubility plays a critical role in drug effectiveness. Without it, a drug substance cannot be absorbed, leading to low bioavailability. Poor solubility of drugs also leads to other issues, such as challenges with metabolism or permeability, interactions with other drugs or the need to extend drug release.

How is drug absorbed in the body? ›

After a drug is administered, it is absorbed into the bloodstream. The circulatory system then distributes the drug throughout the body. Then it is metabolized by the body. The drug and its metabolites are then excreted.

Where are drugs absorbed? ›

For these reasons, most drugs are absorbed primarily in the small intestine, and acids, despite their ability as un-ionized drugs to readily cross membranes, are absorbed faster in the intestine than in the stomach (for review, see [ 1 General reference Drug absorption is determined by the drug's physicochemical ...

Why is pharmacology so hard? ›

Studying for pharmacology can be extremely difficult due to the overwhelming amount of information to memorize such as drug side effects, target lab values, drug interactions and more.

What are the 5 steps of pharmacokinetics? ›

Pharmacokinetics is the movement of a drug through the body's biological systems, these processes include absorption, distribution, bioavailability, metabolism, and elimination.

How many years does it take to study pharmacology? ›

Most pharmacologists earn a degree called a Pharm. D., which stands for Doctor of Pharmacy, from a pharmacy school (four years of undergraduate, pre-professional college coursework, plus four years of professional study. It's the same education traditional pharmacists go through.)

What are the different types of drugs? ›

7 Drug Categories
  • (1) Central Nervous System (CNS) Depressants. CNS depressants slow down the operations of the brain and the body. ...
  • (2) CNS Stimulants. ...
  • (3) Hallucinogens. ...
  • (4) Dissociative Anesthetics. ...
  • (5) Narcotic Analgesics. ...
  • (6) Inhalants. ...
  • (7) Cannabis.

What are the 5 branches of pharmacology? ›

Terms in this set (5)
  • Pharmacokinetics. what the body does with the drug after administration.
  • Pharmacodynamics. biochemical and physical effects of drugs & how they work.
  • Pharmacotherapeutics. use of drugs to prevent and treat diseases.
  • Pharmacognosy. study of natural resources of drugs (plants, animals, etc)
  • Toxicology.

What are the source of drugs? ›

Sources of drugs may be natural, synthetic, and biosynthetic. Drugs of plant, animal, microbiological, marine, mineral, geographical origins constitute the natural sources. The entire plant, plant parts, secretion, and exudate of plants are the sources of plant drugs.


1. Pharmacokinetics - Part 2: Lipophilic and Hydrophilic drugs
(AMBOSS: Medical Knowledge Distilled)
2. 20151102 Basic Pharmacokinetic Principles and Pharmacokinetics of IV Drugs Part 1
(University of Kentucky Department of Anesthesiology)
3. Pharmacokinetics part 2: Distribution, Metabolism and Excretion, Animation
(Alila Medical Media)
4. Pharmacokinetics Part 3
(Paul Merritt)
5. Pharmacodynamics - Part 1: How Drugs Act on the Body
(AMBOSS: Medical Knowledge Distilled)
6. Pharmacokinetics Visualized
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