Distribution of drugs MCQs With Answer is an essential study aid for B.Pharm students to master pharmacokinetics and clinical dosing. This set explores how drugs distribute between plasma, interstitial and intracellular compartments, emphasizing key keywords: volume of distribution (Vd), plasma protein binding, tissue binding, blood-brain barrier, lipophilicity, ionization, perfusion- and permeability-limited distribution, and factors altering Vd such as age, obesity, and disease. Questions include Vd calculations, loading dose concepts, compartmental distribution, and clinical implications of altered drug distribution. Each MCQ is designed to deepen conceptual understanding and exam readiness. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What does the volume of distribution (Vd) represent?
- Apparent volume in which the drug is distributed (Vd = total amount of drug / plasma concentration)
- Actual anatomical volume of blood in the body
- Volume of urine excreted per hour carrying the drug
- Volume of liver tissue only
Correct Answer: Apparent volume in which the drug is distributed (Vd = total amount of drug / plasma concentration)
Q2. A drug with very high plasma protein binding generally has which characteristic?
- High free fraction in plasma
- Low apparent Vd due to confinement to plasma
- Rapid renal excretion regardless of binding
- Enhanced blood-brain barrier penetration
Correct Answer: Low apparent Vd due to confinement to plasma
Q3. Which compartment approximates total body water in a 70 kg adult?
- ~3 L
- ~14 L
- ~42 L
- ~70 L
Correct Answer: ~42 L
Q4. Which factor most increases distribution of a lipophilic drug into tissues?
- High plasma protein binding only
- Low membrane permeability
- High tissue perfusion and lipophilicity
- Strong ionization at physiological pH
Correct Answer: High tissue perfusion and lipophilicity
Q5. Vd greater than total body water (e.g., >42 L) implies which of the following?
- Drug is confined to the plasma
- Drug extensively binds to tissues or fat
- Drug is rapidly eliminated renally
- Drug cannot cross cell membranes
Correct Answer: Drug extensively binds to tissues or fat
Q6. Which equation gives the initial volume of distribution after an IV bolus?
- Vd = Dose / AUC
- Vd = Clearance × Half-life
- Vd = Dose / Plasma concentration at time zero (Cp0)
- Vd = Bioavailability × Dose
Correct Answer: Vd = Dose / Plasma concentration at time zero (Cp0)
Q7. What is the primary clinical use of knowing Vd when calculating a loading dose?
- To determine renal clearance
- To calculate the dose required to reach target plasma concentration quickly
- To estimate oral bioavailability
- To measure drug metabolism rate
Correct Answer: To calculate the dose required to reach target plasma concentration quickly
Q8. A drug that is a weak base may accumulate in acidic compartments by which mechanism?
- Protein binding
- Ion trapping
- Active transport out of cells
- Enzymatic degradation
Correct Answer: Ion trapping
Q9. Which statement best describes perfusion-limited distribution?
- Distribution rate is governed by membrane permeability
- Distribution depends primarily on blood flow to the tissue
- Distribution only occurs via active transporters
- Distribution is independent of tissue blood flow
Correct Answer: Distribution depends primarily on blood flow to the tissue
Q10. Which of the following reduces the free (unbound) fraction of a drug in plasma?
- Decreased levels of plasma proteins
- Displacement by a highly protein-bound coadministered drug
- Renal failure without changes in binding
- Increased hepatic metabolism
Correct Answer: Displacement by a highly protein-bound coadministered drug
Q11. Which tissue is most likely to accumulate lipophilic drugs over time?
- Plasma
- Adipose tissue
- Bone marrow
- Extracellular fluid
Correct Answer: Adipose tissue
Q12. P-glycoprotein (P-gp) at the blood-brain barrier primarily affects distribution by:
- Increasing passive diffusion into the brain
- Actively effluxing drugs out of the brain, limiting CNS penetration
- Binding drugs to plasma proteins
- Enhancing tissue perfusion
Correct Answer: Actively effluxing drugs out of the brain, limiting CNS penetration
Q13. Which value approximates plasma volume in an average adult?
- ~3 L
- ~14 L
- ~28 L
- ~42 L
Correct Answer: ~3 L
Q14. How does hypoalbuminemia affect distribution of acidic drugs that bind albumin?
- Increase free fraction and potentially increase Vd
- Decrease free fraction and decrease Vd
- No change in free fraction
- Prevent drug metabolism entirely
Correct Answer: Increase free fraction and potentially increase Vd
Q15. For a hydrophilic drug that distributes mainly in extracellular fluid, the expected Vd is approximately:
- ~3 L
- ~14 L
- ~42 L
- >100 L
Correct Answer: ~14 L
Q16. Which property most facilitates crossing the blood-brain barrier?
- High polarity and large molecular size
- High lipophilicity and low molecular weight
- Strong binding to plasma proteins
- Strong positive charge at physiological pH
Correct Answer: High lipophilicity and low molecular weight
Q17. A drug displays a very large apparent Vd and a long half-life. Which explanation fits this observation?
- Drug is confined to plasma with low tissue binding
- Drug extensively binds to peripheral tissues and is slowly released
- Drug is rapidly excreted unchanged in urine
- Drug cannot cross cell membranes
Correct Answer: Drug extensively binds to peripheral tissues and is slowly released
Q18. Which factor is LEAST likely to alter the distribution of a drug?
- Changes in plasma protein concentration
- Alterations in tissue perfusion
- Drug’s intrinsic clearance by hepatic enzymes
- Changes in membrane permeability
Correct Answer: Drug’s intrinsic clearance by hepatic enzymes
Q19. Which statement about distribution into breast milk is correct?
- Only highly protein-bound drugs enter breast milk easily
- Weak bases tend to concentrate in breast milk due to ion trapping
- All drugs are excluded from breast milk by the blood-milk barrier
- Lipophilicity does not influence milk transfer
Correct Answer: Weak bases tend to concentrate in breast milk due to ion trapping
Q20. How does obesity typically affect Vd for lipophilic drugs?
- Decrease Vd due to less fat tissue
- No effect on Vd
- Increase Vd because of larger adipose reservoir
- Make Vd equal to plasma volume
Correct Answer: Increase Vd because of larger adipose reservoir
Q21. Which method is commonly used experimentally to estimate Vd?
- Determining urinary excretion over 24 hours only
- Single IV bolus administration and measuring plasma concentration extrapolated to time zero
- Measuring half-life without concentration data
- Measuring stool concentrations only
Correct Answer: Single IV bolus administration and measuring plasma concentration extrapolated to time zero
Q22. A drug that is highly ionized at physiological pH will most likely have:
- High membrane permeability and large Vd
- Poor membrane permeability and distribution largely confined to extracellular fluid
- Enhanced entry into the CNS
- Preferential accumulation in adipose tissue
Correct Answer: Poor membrane permeability and distribution largely confined to extracellular fluid
Q23. Which clinical condition can reduce distribution to tissues by decreasing tissue perfusion?
- Hyperthyroidism
- Congestive heart failure with poor cardiac output
- Fever with increased cardiac output
- Acute exercise
Correct Answer: Congestive heart failure with poor cardiac output
Q24. In two-compartment kinetics, the initial rapid decline in plasma concentration mainly reflects:
- Elimination from the central compartment only
- Distribution of drug from central to peripheral compartment
- Complete absorption of oral dose
- Metabolic activation to an active metabolite
Correct Answer: Distribution of drug from central to peripheral compartment
Q25. Which statement best describes tissue binding impact on drug clearance?
- Tissue binding always increases renal clearance
- Extensive tissue binding can act as a reservoir, prolonging apparent half-life and delaying clearance
- Tissue binding converts drug into inactive metabolites immediately
- Tissue binding has no impact on pharmacokinetics
Correct Answer: Extensive tissue binding can act as a reservoir, prolonging apparent half-life and delaying clearance
Q26. Which parameter must you know to calculate a loading dose?
- Vd and desired plasma concentration
- Only half-life
- Only renal clearance
- Total urine output
Correct Answer: Vd and desired plasma concentration
Q27. Which of the following best explains why basic drugs often concentrate in stomach contents?
- Stomach pH is basic causing enhanced lipophilicity
- Ion trapping of weak bases in acidic gastric fluid
- High protein content of gastric juice binds bases
- Active transport pumps base molecules into lumen
Correct Answer: Ion trapping of weak bases in acidic gastric fluid
Q28. Which scenario will increase free fraction (fu) of a drug in plasma?
- Increased alpha-1-acid glycoprotein levels
- Administration of a competing highly protein-bound drug that displaces it
- Higher albumin concentration
- Increased binding affinity to albumin
Correct Answer: Administration of a competing highly protein-bound drug that displaces it
Q29. Which statement about distribution equilibrium is correct?
- Equilibrium between plasma and tissue concentrations is always achieved instantaneously
- Highly perfused tissues reach equilibrium faster than poorly perfused tissues
- Equilibrium is independent of tissue permeability
- Only active transport can establish equilibrium
Correct Answer: Highly perfused tissues reach equilibrium faster than poorly perfused tissues
Q30. If a drug has a Vd of 5 L, what does this imply clinically?
- Drug is extensively distributed into adipose tissue
- Drug is primarily confined to plasma compartment
- Drug distributes into total body water
- Drug has high CNS penetration
Correct Answer: Drug is primarily confined to plasma compartment

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