Pharmacokinetics in biopharmaceutical development MCQs With Answer

Pharmacokinetics in biopharmaceutical development MCQs With Answer

This collection of MCQs is designed for M.Pharm students focusing on pharmacokinetics (PK) as applied to biopharmaceuticals. The questions explore core and advanced concepts such as absorption pathways for large molecules, FcRn-mediated recycling, target-mediated drug disposition, non-compartmental and compartmental analysis, population PK, immunogenicity effects on clearance, and strategies used in biosimilar PK comparability. Each question emphasizes mechanistic understanding and practical implications for drug development, dosing design, and interpretation of PK data in preclinical and clinical stages. Use these problems to test readiness for research, regulatory submissions, and rational design of biotherapeutic dosing regimens.

Q1. Which pathway is the primary route for systemic absorption of most therapeutic monoclonal antibodies after subcutaneous administration?

• Rapid transcellular diffusion across capillary endothelial cells
• Direct absorption into blood capillaries via paracellular pores
• Lymphatic uptake and drainage into systemic circulation
• Enzymatic cleavage in the interstitium followed by hepatic uptake

Correct Answer: Lymphatic uptake and drainage into systemic circulation

Q2. Which mechanism most commonly explains prolonged half-life of IgG-based biologics in humans?

• Renal filtration of intact IgG is reduced by glycosylation
• Binding to neonatal Fc receptor (FcRn) protecting from lysosomal degradation
• High plasma protein binding to albumin reducing clearance
• Rapid internalization into hepatocytes with slow release

Correct Answer: Binding to neonatal Fc receptor (FcRn) protecting from lysosomal degradation

Q3. Target-mediated drug disposition (TMDD) typically results in which characteristic pharmacokinetic behavior?

• Linear dose-proportional increase in exposure across all doses
• Saturable, nonlinear clearance at therapeutic concentrations
• Exclusive renal elimination with constant half-life
• Immediate equilibrium between plasma and tissue compartments

Correct Answer: Saturable, nonlinear clearance at therapeutic concentrations

Q4. In non-compartmental analysis (NCA), which parameter is directly used to estimate total systemic clearance for intravenous administration?

• Area under the moment curve (AUMC) divided by Cmax
• Volume of distribution at steady state (Vss) times half-life
• Dose divided by area under the plasma concentration–time curve (AUC)
• Terminal slope multiplied by the dosing interval

Correct Answer: Dose divided by area under the plasma concentration–time curve (AUC)

Q5. Which covariate is most frequently significant in population PK models of monoclonal antibodies affecting exposure?

• Patient hair color
• Body weight or body surface area
• Blood cholesterol level
• Daily sodium intake

Correct Answer: Body weight or body surface area

Q6. Anti-drug antibodies (ADAs) can alter the pharmacokinetics of a biologic primarily by which mechanism?

• Increasing renal filtration of the free drug
• Enhancing receptor-mediated drug recycling via FcRn
• Forming immune complexes that increase clearance via reticuloendothelial system
• Converting the drug into an inactive metabolite within plasma

Correct Answer: Forming immune complexes that increase clearance via reticuloendothelial system

Q7. Which statement best describes bioavailability of therapeutic proteins given orally?

• Generally high and similar to parenteral routes due to small molecular size
• Typically very low because of enzymatic degradation and poor mucosal permeability
• Equivalent to subcutaneous administration when co-administered with enzyme inhibitors
• High if formulated as enteric-coated tablets to bypass stomach acid

Correct Answer: Typically very low because of enzymatic degradation and poor mucosal permeability

Q8. When developing a biosimilar, which PK parameter is most commonly used as the primary endpoint in comparative studies?

• Steady-state volume of distribution (Vss)
• Maximum observed concentration (Cmax) and AUC
• Renal clearance normalized to creatinine clearance
• Time to first metabolite appearance

Correct Answer: Maximum observed concentration (Cmax) and AUC

Q9. Which elimination route is generally less important for large proteins such as monoclonal antibodies?

• Proteolytic catabolism in tissues and cells
• FcRn-mediated salvage leading to reduced lysosomal degradation
• Glomerular filtration followed by urinary excretion of intact antibody
• Receptor-mediated endocytosis followed by lysosomal degradation

Correct Answer: Glomerular filtration followed by urinary excretion of intact antibody

Q10. Allometric scaling is commonly used to predict human PK from animal data. Which scaling exponent is typically applied to clearance when using body weight?

• Exponent of 1.0 (linear scaling)
• Exponent of 0.75 (metabolic scaling)
• Exponent of 0.33 (surface area scaling)
• Exponent of 2.0 (quadratic scaling)

Correct Answer: Exponent of 0.75 (metabolic scaling)

Q11. Which analytical consideration is critical when measuring free versus total drug concentrations for monoclonal antibodies in PK studies?

• Using non-specific protein assays that detect all IgG in plasma
• Ensuring assay can discriminate between free drug and drug bound to target or ADA
• Measuring only in whole blood to avoid plasma separation artifacts
• Relying on single time-point measurements for steady-state inference

Correct Answer: Ensuring assay can discriminate between free drug and drug bound to target or ADA

Q12. Which PK feature suggests target-mediated clearance is dominant at low concentrations but saturable at higher concentrations?

• Linear increase of AUC with dose across the entire dose range
• Shorter half-life at high doses compared to low doses
• Nonlinear increase in AUC with increasing dose, greater-than-proportional exposure
• Constant clearance irrespective of dose

Correct Answer: Nonlinear increase in AUC with increasing dose, greater-than-proportional exposure

Q13. Which dosing strategy is most appropriate to rapidly achieve therapeutic concentrations of a biologic with a long half-life?

• Multiple small subcutaneous doses administered hourly
• A single low loading dose followed by no maintenance dosing
• An initial loading dose followed by maintenance dosing at intervals matching the half-life
• Continuous oral administration to maintain steady exposure

Correct Answer: An initial loading dose followed by maintenance dosing at intervals matching the half-life

Q14. Which parameter is directly affected when a monoclonal antibody exhibits high-affinity binding to a membrane-bound target that is expressed widely?

• Apparent volume of distribution is reduced to plasma volume only
• Clearance may increase due to target-mediated internalization and degradation
• Bioavailability after IV administration becomes unpredictable
• Terminal half-life becomes independent of dose

Correct Answer: Clearance may increase due to target-mediated internalization and degradation

Q15. In population PK modeling, which method is commonly used to quantify inter-individual variability on parameters like clearance?

• Use of fixed-effects only without random components
• Inclusion of exponential random effects (η) on parameters
• Applying linear regression without residual error
• Ignoring variability and reporting mean values only

Correct Answer: Inclusion of exponential random effects (η) on parameters

Q16. Which factor most strongly influences subcutaneous bioavailability of therapeutic proteins?

• The ambient temperature at the injection site only
• Molecular size, formulation excipients, and local proteolysis
• Presence of hepatic first-pass metabolism enzymes
• Rate of gastric emptying

Correct Answer: Molecular size, formulation excipients, and local proteolysis

Q17. Which statement describes a key regulatory expectation for comparative PK studies of biosimilars?

• Demonstrating identical immunogenicity profiles is unnecessary
• Equivalence margins for PK metrics like AUC and Cmax must be pre-specified and justified
• Only a single-subject crossover design is acceptable
• Non-compartmental analysis is prohibited for biosimilar assessments

Correct Answer: Equivalence margins for PK metrics like AUC and Cmax must be pre-specified and justified

Q18. Which modeling approach is preferred to explicitly characterize nonlinear kinetics due to receptor binding and internalization?

• Simple one-compartment linear model without binding terms
• Target-mediated drug disposition (TMDD) models incorporating binding kinetics
• Non-compartmental analysis only using AUC values
• Empirical exponential decay models ignoring receptor interactions

Correct Answer: Target-mediated drug disposition (TMDD) models incorporating binding kinetics

Q19. Which unit is commonly used to express clearance for therapeutic proteins in clinical PK studies?

• mg/kg/day
• mL/min/kg or L/h/kg
• mol/L^2
• percent per hour (%/h)

Correct Answer: mL/min/kg or L/h/kg

Q20. Therapeutic drug monitoring (TDM) for biologics is most useful when which condition applies?

• There is a wide therapeutic index and no exposure–response relationship
• There is a clear exposure–response or exposure–toxicity relationship and inter-individual PK variability is high
• Drug concentrations are identical in all patients regardless of dose
• TDM is only useful for small-molecule oral drugs, not biologics

Correct Answer: There is a clear exposure–response or exposure–toxicity relationship and inter-individual PK variability is high

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