Protein binding MCQs With Answer is a focused review for B. Pharm students to master drug–protein interactions, plasma protein binding, and their impact on pharmacokinetics and pharmacodynamics. This concise introduction covers key concepts such as albumin and alpha-1-acid glycoprotein binding, free drug fraction, effects of hypoalbuminemia, displacement interactions, and measurement methods like equilibrium dialysis. These protein binding MCQs with answer will help you apply principles to clinical scenarios, drug dosing, and drug interactions, enhancing exam readiness and practical understanding. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is meant by plasma protein binding of a drug?
- Irreversible chemical bonding to plasma proteins
- Reversible binding of drug to plasma proteins reducing free concentration
- Drug metabolism by plasma enzymes
- Active transport of drug into blood cells
Correct Answer: Reversible binding of drug to plasma proteins reducing free concentration
Q2. Which plasma protein primarily binds acidic drugs?
- Alpha-1-acid glycoprotein
- Globulin
- Albumin
- Fibrinogen
Correct Answer: Albumin
Q3. Which protein is more important for basic (cationic) drug binding?
- Albumin
- Alpha-1-acid glycoprotein
- Transferrin
- Fibrinogen
Correct Answer: Alpha-1-acid glycoprotein
Q4. How does high plasma protein binding affect volume of distribution (Vd)?
- Increases Vd markedly
- Decreases Vd because less free drug distributes to tissues
- No change in Vd
- Causes unpredictable increase in tissue binding
Correct Answer: Decreases Vd because less free drug distributes to tissues
Q5. What is the clinical significance of the unbound (free) drug concentration?
- Only total drug concentration determines effect
- Free concentration represents pharmacologically active fraction
- Free drug is always inactive
- Free concentration affects only renal excretion, not effect
Correct Answer: Free concentration represents pharmacologically active fraction
Q6. Which method is commonly used to measure unbound drug concentration?
- Equilibrium dialysis
- Mass spectrometry without separation
- Direct spectrophotometry of whole plasma
- Immunoassay for total protein
Correct Answer: Equilibrium dialysis
Q7. What does a high association constant (Ka) indicate about drug–protein binding?
- Weak binding between drug and protein
- Very rapid dissociation
- Strong binding affinity of drug for protein
- Irreversible binding
Correct Answer: Strong binding affinity of drug for protein
Q8. Which clinical condition commonly decreases albumin concentration and increases free fraction of acidic drugs?
- Hyperproteinemia
- Hypoalbuminemia due to liver disease
- Dehydration
- Polycythemia
Correct Answer: Hypoalbuminemia due to liver disease
Q9. What is the effect of displacement of a highly protein-bound drug by another drug?
- Decrease in free drug concentration and reduced effect
- Transient increase in free drug concentration and potential toxicity
- No change in free concentration because total drug remains same
- Permanent loss of binding sites
Correct Answer: Transient increase in free drug concentration and potential toxicity
Q10. Which of the following drugs is classically highly albumin bound?
- Gentamicin
- Warfarin
- Metformin
- Digoxin
Correct Answer: Warfarin
Q11. How does renal failure affect plasma protein binding of some drugs?
- Increases albumin concentration and reduces free drug
- Can decrease binding due to accumulation of uremic toxins that compete for binding
- Has no effect on protein binding
- Eliminates all protein binding
Correct Answer: Can decrease binding due to accumulation of uremic toxins that compete for binding
Q12. Which statement about equilibrium dialysis is true?
- It measures total drug concentration directly
- It separates free drug and protein-bound drug across a semi-permeable membrane
- It requires ultracentrifugation of plasma
- It measures only protein concentration
Correct Answer: It separates free drug and protein-bound drug across a semi-permeable membrane
Q13. What does the term ‘fraction unbound (fu)’ indicate?
- Fraction of drug irreversibly bound to tissues
- Proportion of total drug in plasma that is free and pharmacologically active
- Percentage of drug excreted unchanged
- Percentage metabolized by liver
Correct Answer: Proportion of total drug in plasma that is free and pharmacologically active
Q14. How does hypoalbuminemia influence dosing of highly albumin-bound drugs?
- No dosing change is ever needed
- May require dose reduction due to higher free concentrations and toxicity risk
- Always requires dose increase to achieve effect
- Only affects oral but not IV dosing
Correct Answer: May require dose reduction due to higher free concentrations and toxicity risk
Q15. Which kinetic assumption is true for linear protein binding?
- Binding sites are saturable at therapeutic concentrations
- Fraction bound is constant and independent of concentration
- Binding increases exponentially with concentration
- Protein binding leads to irreversible removal
Correct Answer: Fraction bound is constant and independent of concentration
Q16. Saturable protein binding leads to which type of pharmacokinetic behavior?
- Linear pharmacokinetics
- Nonlinear pharmacokinetics with concentration-dependent free fraction
- Zero-order elimination at all concentrations
- No change in free fraction with dose
Correct Answer: Nonlinear pharmacokinetics with concentration-dependent free fraction
Q17. Which parameter increases when free drug fraction increases, assuming clearance of free drug remains constant?
- Total plasma concentration decreases
- Total clearance decreases
- Free drug clearance increases proportionally to fu
- Volume of distribution becomes zero
Correct Answer: Free drug clearance increases proportionally to fu
Q18. The Scatchard plot is used to determine which of the following?
- Absolute bioavailability
- Binding affinity and number of binding sites on a protein
- Renal clearance
- Protein synthesis rate
Correct Answer: Binding affinity and number of binding sites on a protein
Q19. Which term describes the dissociation constant of drug–protein complex?
- Vmax
- Kd
- fu
- Cl
Correct Answer: Kd
Q20. Why are drugs with high protein binding more susceptible to drug–drug displacement interactions?
- Because they are water soluble
- Because a small change in bound fraction causes large relative change in unbound concentration
- They are less likely to be metabolized
- They are mainly excreted unchanged
Correct Answer: Because a small change in bound fraction causes large relative change in unbound concentration
Q21. Which laboratory condition can artifactually alter measured protein binding?
- Maintaining physiologic temperature and pH
- Using hemolyzed plasma with altered pH
- Using ultraclean non-protein matrices
- Ensuring sample-to-buffer ratio is correct
Correct Answer: Using hemolyzed plasma with altered pH
Q22. Which drug is known for high affinity to alpha-1-acid glycoprotein?
- Warfarin
- Lidocaine
- Gentamicin
- Metformin
Correct Answer: Lidocaine
Q23. How does pregnancy generally affect drug protein binding?
- Increased albumin leading to lower free fraction of acidic drugs
- Decreased albumin and increased free fraction of highly albumin-bound drugs
- No change in protein levels during pregnancy
- Permanent loss of binding proteins
Correct Answer: Decreased albumin and increased free fraction of highly albumin-bound drugs
Q24. In hypoalbuminemia, total drug concentration may be low while unbound concentration is
- Also low and clinically insignificant
- Unchanged and clinically irrelevant
- Normal or increased, potentially causing toxicity
- Completely eliminated
Correct Answer: Normal or increased, potentially causing toxicity
Q25. Which effect does increased free fraction usually have on drug clearance for low extraction ratio drugs?
- No change because clearance is independent of fu
- Clearance increases because hepatic clearance depends on free concentration
- Clearance decreases due to saturation
- Renal clearance becomes zero
Correct Answer: Clearance increases because hepatic clearance depends on free concentration
Q26. Ultrafiltration separates free drug from bound drug based on which principle?
- Size exclusion through a membrane allowing only free drug to pass
- Centrifugal precipitation of proteins
- Chemical denaturation of proteins
- Selective antibody capture of bound drug
Correct Answer: Size exclusion through a membrane allowing only free drug to pass
Q27. Which of the following drugs has relatively low plasma protein binding?
- Phenytoin
- Diazepam
- Gentamicin
- Warfarin
Correct Answer: Gentamicin
Q28. A drug with fu = 0.05 is considered:
- Minimally bound to plasma proteins
- Highly protein bound
- Completely unbound
- Irreversibly bound
Correct Answer: Highly protein bound
Q29. Which factor does NOT usually affect plasma protein binding?
- pH of plasma
- Concentration of binding proteins
- Ambient lighting in the laboratory
- Presence of competing ligands
Correct Answer: Ambient lighting in the laboratory
Q30. In acute inflammation, alpha-1-acid glycoprotein levels typically:
- Decrease markedly
- Increase, affecting basic drug binding
- Remain unchanged
- Are eliminated
Correct Answer: Increase, affecting basic drug binding
Q31. Which parameter is directly measured during a protein binding study by equilibrium dialysis?
- Total plasma protein concentration
- Free drug concentration in dialysate at equilibrium
- Number of binding sites on albumin
- Metabolite structures
Correct Answer: Free drug concentration in dialysate at equilibrium
Q32. For a highly protein-bound drug, what is the immediate effect of administering a competing drug that displaces binding?
- Permanent increase in total drug concentration
- Transient rise in free drug concentration while total remains similar
- Immediate elimination of both drugs
- Irreversible protein denaturation
Correct Answer: Transient rise in free drug concentration while total remains similar
Q33. Which mathematical relationship links free fraction (fu), bound drug, and total concentration?
- fu = free concentration / total concentration
- fu = total concentration / free concentration
- fu = bound concentration / free concentration
- fu = Vd × clearance
Correct Answer: fu = free concentration / total concentration
Q34. A decrease in protein binding will generally cause what change in drug half-life for drugs cleared proportionally to free concentration?
- Half-life increases because total concentration rises
- Half-life decreases because free fraction and clearance increase
- Half-life remains constant regardless of fu
- Half-life becomes infinite
Correct Answer: Half-life decreases because free fraction and clearance increase
Q35. Which experimental artifact can lead to underestimation of protein binding in vitro?
- Maintaining physiological temperature during assay
- Diluting plasma excessively before measurement
- Using fresh plasma
- Using appropriate controls
Correct Answer: Diluting plasma excessively before measurement
Q36. Which drug class often shows concentration-dependent (saturable) protein binding at therapeutic ranges?
- Low protein-binding antibiotics like aminoglycosides
- Highly protein-bound drugs like phenytoin at high concentrations
- Purely renal-excreted small molecules
- All beta blockers
Correct Answer: Highly protein-bound drugs like phenytoin at high concentrations
Q37. In clinical monitoring of highly protein-bound drugs, what measurement is most informative?
- Total plasma concentration only
- Unbound (free) drug concentration especially in altered protein states
- Serum electrolyte levels
- Urine color and volume
Correct Answer: Unbound (free) drug concentration especially in altered protein states
Q38. Which of the following decreases the protein binding of acidic drugs?
- Increase in albumin concentration
- Competitive displacement by another acidic drug
- Alkalinization of plasma improving binding
- Higher affinity binding to globulins
Correct Answer: Competitive displacement by another acidic drug
Q39. The law of mass action applied to protein binding implies that at equilibrium:
- Rate of association equals rate of dissociation
- Only association occurs
- Only dissociation occurs
- No binding occurs at equilibrium
Correct Answer: Rate of association equals rate of dissociation
Q40. Why is it important to consider protein binding in dose adjustment for elderly patients?
- Elderly always have higher albumin so dose must increase
- Age-related changes in protein levels and competing medications can alter free drug and increase toxicity risk
- Protein binding is irrelevant in elderly
- Only renal function matters in elderly
Correct Answer: Age-related changes in protein levels and competing medications can alter free drug and increase toxicity risk
Q41. Binding to which site on albumin is commonly involved in warfarin interaction?
- Sudlow site I
- Sudlow site II
- Heme-binding site
- Metal-binding site
Correct Answer: Sudlow site I
Q42. Which clinical scenario can increase alpha-1-acid glycoprotein and alter drug binding?
- Acute inflammation or infection
- Severe malnutrition decreasing all proteins
- Chronic hypothermia
- Dehydration without inflammation
Correct Answer: Acute inflammation or infection
Q43. For a drug primarily cleared by the liver and highly protein-bound, a decrease in protein binding will most likely:
- Decrease hepatic clearance
- Increase hepatic clearance if intrinsic clearance is capacity-limited
- Have no effect on hepatic clearance
- Completely prevent hepatic metabolism
Correct Answer: Increase hepatic clearance if intrinsic clearance is capacity-limited
Q44. Which experimental technique uses centrifugal force to separate free and bound drug?
- Equilibrium dialysis
- Ultrafiltration
- Ultracentrifugation
- Spectrophotometry
Correct Answer: Ultracentrifugation
Q45. How does pH affect drug–protein binding?
- pH only affects drug solubility, not binding
- Changes in pH can alter ionization of drug and protein, modifying binding affinity
- All drugs bind equally regardless of pH
- pH only affects transporters, not protein interactions
Correct Answer: Changes in pH can alter ionization of drug and protein, modifying binding affinity
Q46. In therapeutic drug monitoring of phenytoin in hypoalbuminemia, which is most appropriate?
- Rely solely on total phenytoin concentration
- Measure free phenytoin concentration or adjust total concentration for low albumin
- Ignore protein binding and halve the dose
- Double the dose to compensate for low total levels
Correct Answer: Measure free phenytoin concentration or adjust total concentration for low albumin
Q47. Which of the following best describes ‘binding capacity’ of plasma protein?
- Maximum number of drug molecules that a protein molecule can bind
- Rate at which drug is metabolized
- Plasma volume available for drug distribution
- Liver’s capacity to synthesize proteins
Correct Answer: Maximum number of drug molecules that a protein molecule can bind
Q48. When a second drug displaces the first from protein binding, long-term clinical effects depend on:
- Only the new total concentration of the first drug
- Changes in free concentration and compensatory changes in clearance and distribution
- Immediate permanent increase in tissue binding
- Complete excretion of the first drug
Correct Answer: Changes in free concentration and compensatory changes in clearance and distribution
Q49. Which of the following statements is true about measuring protein binding in vitro vs in vivo?
- In vitro measurements always perfectly predict in vivo binding
- Differences in protein composition, metabolites, and conditions can make in vitro results differ from in vivo
- In vivo binding can be ignored if in vitro data exist
- In vitro methods measure only metabolites
Correct Answer: Differences in protein composition, metabolites, and conditions can make in vitro results differ from in vivo
Q50. Which practical consideration is important when interpreting total drug concentrations in patients with altered protein binding?
- Total concentration alone is sufficient for dose decisions regardless of protein status
- Free (unbound) drug concentration or adjusted total concentration should guide therapy when protein binding is altered
- Protein binding never changes in disease states
- Only urine drug levels matter in these patients
Correct Answer: Free (unbound) drug concentration or adjusted total concentration should guide therapy when protein binding is altered
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
Mail- Sachin@pharmacyfreak.com