Welcome, PharmD students, to this MCQ quiz on Compartmental Models in Pharmacokinetics! To describe and predict a drug’s behavior in the body, pharmacokineticists often use compartmental models. These models simplify the complex physiological system into one or more conceptual compartments, helping us understand drug distribution and elimination patterns. This quiz will test your knowledge of one-compartment, two-compartment, and multi-compartment models, their assumptions, characteristic concentration-time profiles, and their significance in drug therapy. Let’s explore these essential modeling concepts!
1. In pharmacokinetics, a “compartment” is best defined as:
- a) A specific anatomical organ in the body.
- b) A group of tissues or fluids that have similar drug distribution characteristics, considered as a single kinetic unit.
- c) The dosage form of the drug.
- d) The route of drug administration.
Answer: b) A group of tissues or fluids that have similar drug distribution characteristics, considered as a single kinetic unit.
2. The primary purpose of using compartmental models in pharmacokinetics is to:
- a) Determine the chemical structure of a drug.
- b) Describe and predict the concentration-time course of a drug in the body.
- c) Identify the drug’s mechanism of action.
- d) Assess the drug’s manufacturing quality.
Answer: b) Describe and predict the concentration-time course of a drug in the body.
3. A one-compartment open model assumes that a drug, upon administration:
- a) Distributes slowly into multiple distinct tissue compartments.
- b) Distributes rapidly and uniformly throughout the body, which acts as a single, homogenous unit.
- c) Remains only in the bloodstream and does not distribute.
- d) Is eliminated before it can distribute.
Answer: b) Distributes rapidly and uniformly throughout the body, which acts as a single, homogenous unit.
4. Following an intravenous (IV) bolus dose of a drug that fits a one-compartment model and undergoes first-order elimination, the plasma drug concentration declines:
- a) Linearly over time.
- b) Mono-exponentially over time.
- c) Bi-exponentially over time.
- d) In a zero-order fashion.
Answer: b) Mono-exponentially over time.
5. The equation Ct = C0 * e^(-kt) describes the plasma concentration of a drug at time ‘t’ for which model and administration route?
- a) Two-compartment model, oral administration.
- b) One-compartment model, IV bolus administration.
- c) One-compartment model, continuous IV infusion.
- d) Two-compartment model, IV bolus administration.
Answer: b) One-compartment model, IV bolus administration.
6. A key assumption of the two-compartment open model is that the body can be divided into:
- a) An absorption compartment and an elimination compartment.
- b) A central compartment (e.g., blood, highly perfused organs) and a peripheral compartment (e.g., less perfused tissues).
- c) Only an oral compartment and a systemic compartment.
- d) Multiple peripheral compartments but no central compartment.
Answer: b) A central compartment (e.g., blood, highly perfused organs) and a peripheral compartment (e.g., less perfused tissues).
7. Following an IV bolus dose of a drug that fits a two-compartment model, the plasma drug concentration-time profile on a semi-log plot typically shows:
- a) A single straight line.
- b) A curve consisting of two distinct linear phases (bi-exponential decline).
- c) A curve with three distinct linear phases.
- d) A horizontal line indicating constant concentration.
Answer: b) A curve consisting of two distinct linear phases (bi-exponential decline).
8. In a two-compartment model, the initial rapid decline in plasma drug concentration after an IV bolus is primarily due to:
- a) Drug elimination from the central compartment only.
- b) Drug distribution from the central compartment to the peripheral compartment.
- c) Drug absorption.
- d) Saturation of metabolic enzymes.
Answer: b) Drug distribution from the central compartment to the peripheral compartment.
9. The slower, terminal decline phase in a two-compartment model plasma concentration-time curve primarily reflects:
- a) Drug absorption.
- b) Drug distribution equilibrium.
- c) Drug elimination from the central compartment after distribution equilibrium (or pseudo-equilibrium) is approached.
- d) Zero-order elimination.
Answer: c) Drug elimination from the central compartment after distribution equilibrium (or pseudo-equilibrium) is approached.
10. The rate constants k12 and k21 in a two-compartment model describe:
- a) The rates of drug absorption and elimination, respectively.
- b) The rates of drug transfer between the central and peripheral compartments.
- c) The rates of drug metabolism and renal excretion, respectively.
- d) The rates of protein binding and dissociation.
Answer: b) The rates of drug transfer between the central and peripheral compartments.
11. The volume of the central compartment (Vc or V1) in a two-compartment model typically represents:
- a) Total body water.
- b) The volume of plasma and highly perfused tissues where the drug initially distributes.
- c) The volume of the peripheral compartment.
- d) The sum of all physiological fluid volumes.
Answer: b) The volume of plasma and highly perfused tissues where the drug initially distributes.
12. The hybrid rate constant ‘alpha’ (α) in a two-compartment model is larger than ‘beta’ (β) and primarily reflects the:
- a) Absorption phase.
- b) Terminal elimination phase.
- c) Distribution phase (and some elimination).
- d) Zero-order input rate.
Answer: c) Distribution phase (and some elimination).
13. The hybrid rate constant ‘beta’ (β) in a two-compartment model is smaller than ‘alpha’ (α) and primarily reflects the:
- a) Initial distribution phase.
- b) Terminal elimination phase, once distribution is largely complete.
- c) Absorption rate.
- d) Rate of drug input.
Answer: b) Terminal elimination phase, once distribution is largely complete.
14. Which volume of distribution term in a two-compartment model is usually the largest and is used for calculating clearance (CL = β * Varea)?
- a) Vc (Volume of central compartment)
- b) Vp (Volume of peripheral compartment)
- c) Vss (Volume of distribution at steady state)
- d) Varea or Vβ (Volume of distribution by area)
Answer: d) Varea or Vβ (Volume of distribution by area)
15. A drug is more likely to be described by a two-compartment model (rather than one-compartment) if it:
- a) Distributes very rapidly and homogeneously throughout the body.
- b) Distributes slowly into certain tissues, leading to a discernible distribution phase.
- c) Is eliminated only by the kidneys.
- d) Has very low plasma protein binding.
Answer: b) Distributes slowly into certain tissues, leading to a discernible distribution phase.
16. The number of exponential terms required to describe the plasma concentration-time curve after an IV bolus indicates the number of kinetically distinguishable:
- a) Routes of administration.
- b) Metabolic pathways.
- c) Compartments in the model.
- d) Doses given.
Answer: c) Compartments in the model. (e.g., one term for one-compartment, two terms for two-compartment)
17. Compared to a one-compartment model, a two-compartment model provides a more accurate description for drugs that exhibit:
- a) No tissue distribution.
- b) A slower equilibration between blood and some less well-perfused tissues.
- c) Only renal elimination.
- d) Zero-order absorption.
Answer: b) A slower equilibration between blood and some less well-perfused tissues.
18. The volume of distribution at steady state (Vss) in a multi-compartment model represents:
- a) The volume of the central compartment only.
- b) The sum of the volumes of all compartments at distribution equilibrium.
- c) The volume calculated using the terminal elimination rate constant.
- d) The volume into which the drug would have to distribute to give the Css if the entire body were at that concentration.
Answer: d) The volume into which the drug would have to distribute to give the Css if the entire body were at that concentration. (More precisely, Vss = Amount in body at steady state / Concentration in plasma at steady state)
19. What is a limitation of using highly complex multi-compartment models (e.g., three or more compartments)?
- a) They are always less accurate than one-compartment models.
- b) The physiological meaning of each compartment becomes clearer.
- c) They often require more data points to accurately estimate parameters and may be overly complex for practical clinical use.
- d) They can only be used for orally administered drugs.
Answer: c) They often require more data points to accurately estimate parameters and may be overly complex for practical clinical use.
20. The choice of which compartmental model to use for a particular drug is often based on:
- a) The drug’s color and odor.
- b) How well the model fits the experimental concentration-time data and its ability to predict future concentrations.
- c) The cost of the drug.
- d) The preference of the pharmaceutical company.
Answer: b) How well the model fits the experimental concentration-time data and its ability to predict future concentrations.
21. In a one-compartment model, the elimination rate constant (k or k10) represents elimination from:
- a) The peripheral compartment.
- b) The central (and only) compartment.
- c) The absorption site.
- d) The gut lumen.
Answer: b) The central (and only) compartment.
22. For a drug best described by a two-compartment model, using a one-compartment model to estimate Vd based on early time points after an IV bolus would likely result in:
- a) An overestimation of the true Vd (e.g., Vss or Vβ).
- b) An underestimation of the true Vd, as it would primarily reflect Vc.
- c) No difference in the Vd estimate.
- d) An estimation of clearance instead of Vd.
Answer: b) An underestimation of the true Vd, as it would primarily reflect Vc.
23. The “method of residuals” or “feathering” is a graphical technique used to resolve the individual exponential terms from a bi-exponential or multi-exponential plasma concentration-time curve, typically to estimate parameters for:
- a) Zero-order absorption.
- b) A one-compartment model.
- c) A two-compartment (or multi-compartment) model.
- d) Protein binding.
Answer: c) A two-compartment (or multi-compartment) model.
24. The transfer rate constant k10 in a two-compartment model represents elimination from:
- a) The peripheral compartment to outside the body.
- b) The central compartment to outside the body.
- c) The peripheral compartment to the central compartment.
- d) The central compartment to the peripheral compartment.
Answer: b) The central compartment to outside the body.
25. Which statement best contrasts the assumptions of one- and two-compartment models regarding drug distribution?
- a) Both assume slow distribution to all tissues.
- b) The one-compartment model assumes instantaneous distribution throughout the body, while the two-compartment model considers a distinct, slower distribution phase into a peripheral compartment.
- c) The two-compartment model assumes instantaneous distribution, while the one-compartment model involves a slow distribution phase.
- d) Neither model considers drug distribution.
Answer: b) The one-compartment model assumes instantaneous distribution throughout the body, while the two-compartment model considers a distinct, slower distribution phase into a peripheral compartment.
26. If the concentration of a drug in a peripheral tissue declines more slowly than in the central compartment, it might act as a:
- a) Site of rapid elimination.
- b) Reservoir, leading to a prolonged terminal elimination phase.
- c) Barrier to initial distribution.
- d) Primary site of absorption.
Answer: b) Reservoir, leading to a prolonged terminal elimination phase.
27. For drugs exhibiting multi-compartment kinetics, the initial Vd (Vc) is often smaller than:
- a) Plasma volume.
- b) The Vd calculated from the terminal elimination phase (Varea or Vβ) or Vss.
- c) Zero.
- d) The dose administered.
Answer: b) The Vd calculated from the terminal elimination phase (Varea or Vβ) or Vss.
28. The terms A and B in the bi-exponential equation Ct = Ae^(-αt) + Be^(-βt) are:
- a) Rate constants for distribution and elimination.
- b) Zero-order intercepts for the distribution and elimination phases, respectively (related to initial amounts in hypothetical compartments).
- c) Volumes of the central and peripheral compartments.
- d) Clearance values.
Answer: b) Zero-order intercepts for the distribution and elimination phases, respectively (related to initial amounts in hypothetical compartments).
29. Why might a drug that is highly lipid-soluble and distributes extensively into adipose tissue be better described by a multi-compartment model than a one-compartment model?
- a) Because adipose tissue is highly perfused.
- b) Because distribution into and out of poorly perfused adipose tissue is slow, creating kinetically distinct compartments.
- c) Because lipid-soluble drugs are not eliminated.
- d) Because one-compartment models only apply to water-soluble drugs.
Answer: b) Because distribution into and out of poorly perfused adipose tissue is slow, creating kinetically distinct compartments.
30. A key implication of a drug following two-compartment kinetics is that peak tissue concentrations (especially in the peripheral compartment) may occur _______ peak plasma concentrations.
- a) at the same time as
- b) later than
- c) earlier than
- d) never, as tissue concentrations are always lower
Answer: b) later than
31. The sum of the amounts of drug in all compartments at any time ‘t’ equals the:
- a) Amount of drug eliminated up to time ‘t’.
- b) Total amount of drug in the body at time ‘t’.
- c) Dose administered.
- d) Steady-state concentration.
Answer: b) Total amount of drug in the body at time ‘t’.
32. In practice, the simplest adequate compartmental model is usually chosen to describe a drug’s pharmacokinetics. This principle is known as:
- a) The law of diminishing returns.
- b) The principle of parsimony (Occam’s Razor).
- c) The bioavailability rule.
- d) The first-pass effect.
Answer: b) The principle of parsimony (Occam’s Razor).
33. If a drug’s plasma concentration-time curve after an IV bolus shows a very rapid initial drop followed by a much slower decline when plotted on semi-log paper, this is indicative of at least a:
- a) Zero-order model.
- b) One-compartment model.
- c) Two-compartment model.
- d) Non-compartmental model.
Answer: c) Two-compartment model.
34. For a one-compartment model, the rate of change of drug in the body (dX/dt) after an IV bolus is described by:
- a) dX/dt = kaXa – kX
- b) dX/dt = -k*X (where X is amount of drug in the body)
- c) dX/dt = R0 – k*X
- d) dX/dt = k12X1 – k21X2 – k10*X1
Answer: b) dX/dt = -k*X (where X is amount of drug in the body)
35. The micro-constants (k10, k12, k21) in a two-compartment model represent:
- a) Overall elimination and distribution rates.
- b) First-order rate constants for drug transfer between compartments and elimination from the central compartment.
- c) Zero-order rate constants.
- d) Hybrid rate constants.
Answer: b) First-order rate constants for drug transfer between compartments and elimination from the central compartment.
36. Volume of distribution by area (Varea or Vβ) is calculated as:
- a) Dose / (α * AUC)
- b) Dose / (β * AUC) or CL / β
- c) Vc + Vp
- d) Dose / A + B
Answer: b) Dose / (β * AUC) or CL / β (CL = Dose/AUC. So Varea = (Dose/AUC)/β = CL/β)
37. The volume of distribution at steady state (Vss) is considered a more physiologically relevant parameter than Vc because it reflects:
- a) Only plasma volume.
- b) The distribution of the drug when an equilibrium between compartments is achieved during constant infusion or at the average concentration during multiple dosing.
- c) The initial rapid distribution.
- d) The volume based on the terminal elimination rate.
Answer: b) The distribution of the drug when an equilibrium between compartments is achieved during constant infusion or at the average concentration during multiple dosing.
38. A three-compartment model might be necessary for drugs that distribute into:
- a) Only plasma.
- b) Plasma and one type of tissue.
- c) Plasma, a rapidly equilibrating (shallow) tissue compartment, and a slowly equilibrating (deep) tissue compartment.
- d) Only adipose tissue.
Answer: c) Plasma, a rapidly equilibrating (shallow) tissue compartment, and a slowly equilibrating (deep) tissue compartment.
39. The main difference in drug elimination assumption between one- and two-compartment models is that:
- a) Elimination only occurs in the one-compartment model.
- b) Elimination only occurs from the peripheral compartment in the two-compartment model.
- c) Elimination is generally assumed to occur from the central compartment in both models (or the sole compartment in the one-compartment model).
- d) Elimination follows zero-order kinetics in the two-compartment model.
Answer: c) Elimination is generally assumed to occur from the central compartment in both models (or the sole compartment in the one-compartment model).
40. If a drug shows a prolonged terminal elimination phase that doesn’t align with its known rapid metabolism, it might suggest:
- a) It fits a one-compartment model perfectly.
- b) Slow release from a deep tissue compartment is rate-limiting its elimination from plasma (indicative of multi-compartment kinetics).
- c) Zero-order absorption.
- d) The drug is not being eliminated.
Answer: b) Slow release from a deep tissue compartment is rate-limiting its elimination from plasma (indicative of multi-compartment kinetics).
41. For drugs with significant distribution into tissues (multi-compartment drugs), plasma concentrations immediately after an IV bolus may not accurately reflect concentrations at the site of action in those tissues because:
- a) Plasma concentration is always higher than tissue concentration.
- b) Distribution equilibrium takes time to achieve.
- c) The drug is instantly eliminated from tissues.
- d) The drug only acts in the plasma.
Answer: b) Distribution equilibrium takes time to achieve.
42. Which of the following is an assumption of all basic compartmental models discussed (one- and two-compartment)?
- a) Drug elimination is always zero-order.
- b) Drug absorption is always instantaneous.
- c) The rate of drug transfer between compartments and the rate of elimination are proportional to the amount (or concentration) of drug in the compartment from which they exit (first-order processes).
- d) The volume of distribution is always equal to total body water.
Answer: c) The rate of drug transfer between compartments and the rate of elimination are proportional to the amount (or concentration) of drug in the compartment from which they exit (first-order processes).
43. The half-life associated with the alpha (α) phase in a two-compartment model (t½α) is _______ the half-life associated with the beta (β) phase (t½β).
- a) longer than
- b) shorter than
- c) equal to
- d) unrelated to
Answer: b) shorter than (Since α > β)
44. The terminal elimination half-life (t½β) in a two-compartment model is often the most clinically relevant half-life for determining:
- a) The rate of initial distribution.
- b) Dosing intervals and time to reach steady state during multiple dosing.
- c) Only the volume of the central compartment.
- d) The absorption rate.
Answer: b) Dosing intervals and time to reach steady state during multiple dosing.
45. A key clinical implication of a drug following two-compartment kinetics is that a loading dose based solely on Vc might initially:
- a) Under-predict the required dose to fill peripheral tissues.
- b) Achieve desired concentrations in both central and peripheral compartments immediately.
- c) Lead to sub-therapeutic levels in the central compartment but rapidly saturate peripheral tissues.
- d) Not be necessary for such drugs.
Answer: a) Under-predict the required dose to fill peripheral tissues. (A loading dose might be calculated as LD = Css * Vss, or a two-part loading dose strategy might be used.) If calculated as Css * Vc, it will only fill the central compartment initially.
Revised Question 45: 45. If a loading dose for a two-compartment drug is calculated using only Vc (volume of central compartment) to achieve a target plasma concentration, what might be observed?
- a) The plasma concentration will remain at the target indefinitely.
- b) The plasma concentration may initially reach the target but then decline as the drug distributes into the peripheral compartment, before rising again with maintenance doses.
- c) The plasma concentration will slowly rise to the target without an initial peak.
- d) The peripheral compartment will be saturated immediately.
Answer: b) The plasma concentration may initially reach the target but then decline as the drug distributes into the peripheral compartment, before rising again with maintenance doses.
46. Compartmental models are simplifications of complex physiological reality. Their utility lies in:
- a) Perfectly mimicking every physiological detail.
- b) Providing a mathematical framework to describe drug disposition, make predictions, and design rational dosing regimens.
- c) Eliminating all inter-individual variability.
- d) Making pharmacokinetics more complicated than it is.
Answer: b) Providing a mathematical framework to describe drug disposition, make predictions, and design rational dosing regimens.
47. The most common method to determine if a drug follows one- or multi-compartment kinetics after an IV bolus is by:
- a) Tasting the drug.
- b) Observing the patient’s therapeutic response.
- c) Analyzing the shape of the plasma concentration-time curve (e.g., on a semi-log plot).
- d) Measuring the drug’s protein binding.
Answer: c) Analyzing the shape of the plasma concentration-time curve (e.g., on a semi-log plot).
48. In a two-compartment model, the amount of drug in the peripheral compartment:
- a) Is always zero.
- b) Increases during the distribution phase and then declines as drug is eliminated from the central compartment (to which it returns).
- c) Only decreases over time.
- d) Remains constant after the initial dose.
Answer: b) Increases during the distribution phase and then declines as drug is eliminated from the central compartment (to which it returns).
49. For drugs fitting a two-compartment model, drug effect might correlate better with concentrations in the:
- a) Central compartment for all drugs and all effects.
- b) Peripheral compartment if that is the site of action, especially if distribution is slow.
- c) Urine.
- d) Stomach.
Answer: b) Peripheral compartment if that is the site of action, especially if distribution is slow.
50. Contrasting one- and two-compartment models, the key difference lies in how they account for:
- a) Drug absorption.
- b) The rate and complexity of drug distribution to various body tissues.
- c) Only drug metabolism.
- d) Only drug excretion.
Answer: b) The rate and complexity of drug distribution to various body tissues.