Drug product performance in vivo MCQs With Answer

Introduction: This collection of multiple-choice questions focuses on drug product performance in vivo, tailored for M.Pharm students studying Modern Bio-Analytical Techniques (MPA 202T). The quiz emphasizes core concepts such as bioavailability, bioequivalence, pharmacokinetic parameters, in vivo study designs, regulatory requirements, and advanced analytical approaches used to evaluate drug performance in humans and animals. Questions probe practical understanding of in vivo methods, interpretation of PK data, IVIVC, PBPK modeling, and analytical strategies like LC-MS/MS and deconvolution. Use these MCQs to test and deepen your comprehension of how in vivo performance is measured, analyzed, and applied to regulatory and research contexts.

Q1. Which pharmacokinetic parameter best reflects the extent of systemic drug exposure following oral administration?

• Maximum plasma concentration (Cmax)
• Time to reach maximum concentration (Tmax)
• Area under the plasma concentration–time curve (AUC)
• Elimination half-life (t1/2)

Correct Answer: Area under the plasma concentration–time curve (AUC)

Q2. What is the principal objective of a bioequivalence study comparing a generic product to a reference product?

• To demonstrate identical pharmacodynamic effects in all patients
• To show equivalent in vitro dissolution profiles only
• To demonstrate similar rate and extent of absorption in vivo
• To prove identical impurity profiles

Correct Answer: To demonstrate similar rate and extent of absorption in vivo

Q3. In a two-period crossover bioequivalence study, which statistical criterion is commonly used to declare bioequivalence for AUC and Cmax?

• p-value less than 0.05 for mean differences
• 90% confidence interval of the geometric mean ratio within 80–125%
• 95% confidence interval of arithmetic mean ratio within 90–110%
• Equivalence shown by overlapping standard deviations

Correct Answer: 90% confidence interval of the geometric mean ratio within 80–125%

Q4. Which of the following best defines absolute bioavailability (F)?

• The fraction of absorbed drug that reaches systemic circulation compared to intravenous administration
• The fraction of drug eliminated unchanged in urine
• The ratio of Cmax to Tmax after oral dosing
• The proportion of drug bound to plasma proteins

Correct Answer: The fraction of absorbed drug that reaches systemic circulation compared to intravenous administration

Q5. IVIVC Level A correlation indicates which of the following?

• A single point correlation between dissolution at one time and plasma concentration
• A qualitative relationship suitable only for immediate-release products
• A point-to-point linear relationship between in vitro dissolution and in vivo input rate
• No predictive value for formulation changes

Correct Answer: A point-to-point linear relationship between in vitro dissolution and in vivo input rate

Q6. Deconvolution in pharmacokinetics is primarily used to:

• Estimate the elimination half-life from a single concentration point
• Determine the in vivo drug input (absorption) rate from plasma concentration-time data
• Transform noncompartmental results into compartmental models directly
• Calculate protein binding from plasma samples

Correct Answer: Determine the in vivo drug input (absorption) rate from plasma concentration-time data

Q7. Which in vivo study design is preferred when between-subject variability is high and a shorter study duration is desired for bioequivalence?

• Parallel design
• Two-period crossover design
• Single ascending dose open-label study
• Case-control observational study

Correct Answer: Two-period crossover design

Q8. In non-compartmental analysis (NCA), which parameter is required to calculate clearance after intravenous dosing?

• Tmax
• AUC0–∞
• Volume of distribution at steady state (Vss)
• Fraction unbound in plasma (fu)

Correct Answer: AUC0–∞

Q9. Which analytical technique is most commonly employed for sensitive quantification of small-molecule drugs in plasma during bioavailability studies?

• UV–Visible spectrophotometry
• LC–MS/MS (liquid chromatography–tandem mass spectrometry)
• Capillary electrophoresis with fluorescence detection
• Immunoassay (ELISA)

Correct Answer: LC–MS/MS (liquid chromatography–tandem mass spectrometry)

Q10. A fed versus fasted study primarily assesses the impact of what on oral drug performance?

• Protein binding changes due to diet
• Food effects on rate and extent of absorption
• Renal clearance variability after meals
• Variations in hepatic enzyme expression over time

Correct Answer: Food effects on rate and extent of absorption

Q11. Which concept explains why two formulations with same AUC but different Cmax could still be considered bioequivalent under certain conditions?

• Therapeutic window and clinical irrelevance of small Tmax differences
• Protein binding equivalence
• Identical excipient composition
• Same route of excretion

Correct Answer: Therapeutic window and clinical irrelevance of small Tmax differences

Q12. Population pharmacokinetic (PopPK) modeling is valuable in in vivo performance because it:

• Requires only in vitro dissolution data to predict in vivo behavior
• Estimates typical PK parameters and quantifies inter-individual variability using sparse sampling
• Eliminates the need for bioequivalence studies
• Directly measures tissue concentrations noninvasively

Correct Answer: Estimates typical PK parameters and quantifies inter-individual variability using sparse sampling

Q13. In bioequivalence testing, why are geometric means and log-transformed data commonly used?

• Concentration data are normally distributed without transformation
• To stabilize variance and account for multiplicative nature of PK parameters
• Because arithmetic means overestimate AUC
• To allow use of nonparametric statistical tests

Correct Answer: To stabilize variance and account for multiplicative nature of PK parameters

Q14. Which is a primary regulatory acceptance criterion for pharmacokinetic equivalence of narrow therapeutic index (NTI) drugs in some jurisdictions?

• Wider bioequivalence bounds such as 75–133%
• Use of 90% CI within tighter limits (e.g., 90–111%) for AUC
• Relaxation of Cmax requirements only
• No requirement for in vivo studies if in vitro dissolution is similar

Correct Answer: Use of 90% CI within tighter limits (e.g., 90–111%) for AUC

Q15. Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug product evaluation because they:

• Rely solely on empirical fitting of clinical data
• Integrate drug-specific properties with physiology to predict in vivo performance in different populations
• Replace the need for analytical quantification methods
• Are only applicable for intravenous drugs

Correct Answer: Integrate drug-specific properties with physiology to predict in vivo performance in different populations

Q16. Which in vivo approach is most appropriate to evaluate the rate of absorption for a rapidly absorbed oral drug when frequent sampling is feasible?

• Measurement of urinary excretion only
• Intensive plasma sampling to accurately determine Cmax and Tmax
• Single blood sample at steady state
• Clinical outcome measures without PK sampling

Correct Answer: Intensive plasma sampling to accurately determine Cmax and Tmax

Q17. For modified-release formulations, which measure is particularly important to assess to ensure consistent in vivo performance?

• Immediate dissolution at 5 minutes only
• Extended-release profile correlation via IVIVC and AUC over the dosing interval
• Only the peak-to-trough ratio at steady state ignoring AUC
• Level of excipient impurities

Correct Answer: Extended-release profile correlation via IVIVC and AUC over the dosing interval

Q18. Which factor can cause a positive bias in observed bioavailability when sampling times miss the true Tmax?

• Using population PK modeling instead of NCA
• Infrequent sampling leading to underestimation of Cmax and misestimation of AUC
• Collecting samples only during elimination phase
• Measuring free drug concentration instead of total drug

Correct Answer: Infrequent sampling leading to underestimation of Cmax and misestimation of AUC

Q19. Which of the following is a typical justification for requesting a biowaiver for a generic immediate-release solid oral dosage form?

• Low permeability and extensive first-pass metabolism
• High solubility and high permeability with rapid in vitro dissolution across media (BCS Class I)
• Complex peptide drug with low oral bioavailability
• Modified-release design intended to alter Tmax

Correct Answer: High solubility and high permeability with rapid in vitro dissolution across media (BCS Class I)

Q20. Metabolite profiling in in vivo performance studies is important because:

• Metabolites never contribute to pharmacological activity
• Regulatory agencies require assessment of major metabolites for safety and exposure comparisons
• It replaces the need to quantify parent drug concentration
• Metabolite data can be used to obviate bioequivalence limits

Correct Answer: Regulatory agencies require assessment of major metabolites for safety and exposure comparisons

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