Toxicokinetics Flashcards
(10 cards)
Regarding the two-compartment model of classic toxicokinetics, which of the following is
true?
a. There is rapid equilibration of chemical between central and peripheral compartments.
b. The logarithm of plasma concentration versus time data yields a linear relationship.
c. There is more than one dispositional phase.
d. It is assumed that the concentration of a chemical is the same throughout the body.
e. It is ineffective in determining effective doses in toxicity studies.
Correct answer: c. There is more than one dispositional phase.
a. FALSE – Rapid equilibration occurs in one-compartment models. In two-compartment models, distribution to the peripheral compartment takes time.
b. FALSE – A semilogarithmic plot gives a curve (not linear) due to the two phases (distribution and elimination).
c. TRUE – The two-compartment model consists of a rapid distribution phase and a slower elimination phase.
d. FALSE – This assumption applies to one-compartment models.
e. FALSE – Two-compartment models are useful in determining effective doses.
When calculating the fraction of a dose remaining in the body over time, which of the
following factors need not be taken into consideration?
a. half-life.
b. initial concentration.
c. time.
d. present concentration.
e. elimination rate constant.
Correct Answer: a. half-life
Explanation:
When calculating the fraction of a dose remaining in the body, you’re working with exponential decay, which depends on the elimination rate constant (k) and time (t):
Fraction remaining = e^(-kt)
So let’s break each option down:
a. half-life – CORRECT ANSWER. While half-life is derived from the elimination rate constant (t½ = 0.693/k), you don’t need to use half-life directly in the fraction equation if you already have k.
b. initial concentration – Needed only if you’re calculating absolute concentration, but for a fraction, the equation normalizes out the initial dose. However, this could be debated depending on framing, which is likely why I originally chose it — but the book is correct: half-life is truly not necessary.
c. time – Definitely needed; it’s one of the two variables in the equation.
d. present concentration – Used to compare against initial if doing dose calculations. Not needed to compute the fraction remaining directly, but helps validate results.
e. elimination rate constant – Essential. It defines the rate at which the substance is cleared.
All of the following statements regarding apparent volume of distribution (Vd) are true
EXCEPT:
a. Vd relates the total amount of chemical in the body to the concentration of chemical in
the plasma.
b. Vd is the apparent space into which an amount of chemical is distributed in the body to
result in a given plasma concentration.
c. A chemical that usually remains in the plasma has a low Vd.
d. Vd will be low for a chemical with high affinity for tissues.
e. Vd can be used to estimate the amount of chemical in the body if the plasma
concentration is known.
d.
a. TRUE – This is the definition of Vd:
Vd = Amount of drug in body / Plasma concentration
b. TRUE – This reflects the conceptual meaning of Vd. It’s an apparent volume, not a physical one, and helps understand how widely a compound distributes.
c. TRUE – If a chemical stays in plasma (doesn’t distribute widely), the Vd is low, often close to plasma volume (~3–5 L).
d. FALSE – A chemical with high tissue affinity leaves the plasma and distributes into tissues — leading to a high Vd, not low.
This is the incorrect (EXCEPT) statement.
e. TRUE – Rearranging the formula:
Amount in body = Vd × plasma concentration
So yes, Vd is used to estimate total body burden.
Chemical clearance:
a. is independent of Vd.
b. is unaffected by kidney failure.
c. is indirectly proportional to Vd.
d. is performed by multiple organs.
e. is not appreciable in the GI tract.
Correct Answer (per the book): d. is performed by multiple organs
That’s true — clearance is a function of multiple organs, primarily liver and kidneys, but also lungs, skin, and others depending on the chemical.
Let’s go through the options:
a. FALSE – Clearance is not independent of Vd. The formula:
Cl = (0.693 × Vd) / t₁/₂
This shows clearance is related to volume of distribution and half-life.
b. FALSE – Kidney failure significantly reduces renal clearance, especially for renally excreted drugs. So this statement is wrong.
c. FALSE – Clearance is directly, not inversely, related to Vd (see formula above). This was my earlier mistake — thanks for catching it!
d. TRUE – Clearance is performed by multiple organs: liver (metabolic clearance), kidneys (renal clearance), and in some cases lungs, skin, bile, or GI tract.
e. FALSE – While GI tract contributes to absorption, it’s not a major route of chemical clearance, so this is technically true but not the most correct or complete compared to option d.
A chemical with which of the following half-lives (T1/2) will remain in the body for the
longest period time when given equal dosage of each?
a. T1/2 = 30 min.
b. T1/2 = 1 day.
c. T1/2 = 7 h.
d. T1/2 = 120 s.
e. T1/2 = 1 month.
Correct answer: e. T1/2 = 1 month
Self-explanatory: the longer the half-life, the longer the duration.
With respect to first-order elimination, which of the following statements is FALSE?
a. The rate of elimination is directly proportional to the amount of the chemical in the
body.
b. A semilogarithmic plot of plasma concentration versus time shows a linear relationship.
c. Half-life (T1/2) differs depending on the dose.
d. Clearance is dosage-independent.
e. The plasma concentration and tissue concentration decrease similarly with respect to the
elimination rate constant
Correct answer: c. Half-life (T1/2) differs depending on the dose.
a. TRUE – That’s the definition of first-order elimination.
b. TRUE – The plot is linear on a semi-log scale.
c. FALSE – In first-order elimination, half-life is constant, independent of dose.
d. TRUE – Clearance is not dose-dependent here.
e. TRUE – Decrease at the same rate over time in plasma and tissue.
The toxicity of a chemical is dependent on the amount of chemical reaching the systemic
circulation. Which of the following does NOT greatly influence systemic availability?
a. absorption after oral dosing.
b. intestinal motility.
c. hepatic first-pass effect.
d. intestinal first-pass effect.
e. incorporation into micelles.
Correct Answer (per the book): b. intestinal motility
Why b is correct:
Intestinal motility refers to how quickly contents move through the gut. While this can affect absorption slightly, it is not a major determinant of systemic availability compared to the other choices. This is why it’s the best answer to the “does NOT greatly influence” part of the question.
Let’s go through all the options:
a. absorption after oral dosing
Very important. If the chemical is not absorbed, it cannot reach the bloodstream.
Strongly influences systemic availability.
NOT the answer.
b. intestinal motility
Can affect how long a chemical stays in the intestine, which may influence absorption rate.
But it’s less critical than first-pass metabolism or actual absorption.
Correct answer – it does not greatly influence systemic availability.
c. hepatic first-pass effect
This can greatly reduce the amount of drug that enters systemic circulation.
Example: drugs like propranolol and morphine undergo extensive first-pass metabolism.
NOT the answer.
d. intestinal first-pass effect
Enterocytes (intestinal cells) contain enzymes (like CYP3A4) that metabolize drugs before they even reach the liver.
Important in reducing systemic availability.
NOT the answer.
e. incorporation into micelles
This is part of lipophilic drug absorption — especially fat-soluble compounds.
Helps solubilize them for transport across the intestinal wall.
Plays a key role in increasing bioavailability.
NOT the answer.
Final Answer:
b. intestinal motility
Which of the following is NOT an advantage of a physiologically based toxicokinetic
model?
a. Complex dosing regimens are easily accommodated.
b. The time course of distribution of chemicals to any organ is obtainable.
c. The effects of changing physiologic parameters on tissue concentrations can be
estimated.
d. The rate constants are obtained from gathered data.
e. The same model can predict toxicokinetics of chemicals across species.
Correct answer: d. The rate constants are obtained from gathered data.
a. TRUE – Models handle complexity.
b. TRUE – Time-course is modeled.
c. TRUE – Parameter manipulation is key strength.
d. FALSE/EXCEPT – Rate constants in these models are estimated, not gathered directly.
e. TRUE – Cross-species prediction is a major use.
Which of the following will not help to increase the flux of a xenobiotic across a biological
membrane?
a. decreased size.
b. decreased oil:water partition coefficient.
c. increased concentration gradient.
d. increased surface area.
e. decreased membrane thickness.
Correct answer: b. decreased oil:water partition coefficient
a. FALSE – Smaller molecules cross more easily.
**b. CORRECT – Decreasing lipophilicity reduces membrane permeability.
c. FALSE – More concentration = more driving force.
d. FALSE – Larger surface area increases flux.
e. FALSE – Thinner membranes improve diffusion.b
Which of the following statements is true regarding diffusion-limited compartments?
a. Xenobiotic transport across the cell membrane is limited by the rate at which blood
arrives at the tissue.
b. Diffusion-limited compartments are also referred to as flow-limited compartments.
c. Increased membrane thickness can cause diffusion-limited xenobiotic uptake.
d. Equilibrium between the extracellular and intracellular space is maintained by rapid
exchange between the two compartments.
e. Diffusion of gases across the alveolar septa of a healthy lung is diffusion-limited.
Correct Answer: c. Increased membrane thickness can cause diffusion-limited xenobiotic uptake
Explanation:
Diffusion-limited uptake refers to when the rate of xenobiotic transfer from blood to tissue is limited by how easily the compound crosses cell membranes, not by blood flow.
Increased membrane thickness = longer diffusion path = slower uptake, which is the core concept in diffusion-limited systems.
Let’s go through each option:
a. Xenobiotic transport is limited by blood flow rate
This describes perfusion-limited (flow-limited), NOT diffusion-limited uptake.
Incorrect.
b. Diffusion-limited = flow-limited
False. These are opposite concepts.
Flow-limited = barrier is easily crossed, rate depends on blood delivery.
Diffusion-limited = barrier is not easily crossed, regardless of flow.
Incorrect.
c. Increased membrane thickness slows uptake
True. This directly limits diffusion rate = diffusion-limited compartment.
Correct answer.
d. Equilibrium is maintained by rapid exchange
This refers more to flow-limited cases.
In diffusion-limited compartments, equilibrium takes longer to reach.
Incorrect.
e. Diffusion of gases in healthy lungs is diffusion-limited
False. In a healthy lung, gas exchange (like O₂ and CO₂) is flow-limited, not diffusion-limited.
Diffusion-limited occurs in diseased states like fibrosis.
Incorrect.
Final Answer:
c. Increased membrane thickness can cause diffusion-limited xenobiotic uptake
