Methods to assess bioavailability MCQs With Answer

Introduction: Methods to assess bioavailability are central to M.Pharm training, bridging formulation science and clinical pharmacokinetics. This collection of MCQs focuses on analytical, experimental, and statistical techniques used to determine how much and how fast a drug reaches systemic circulation. Questions cover in vivo studies (AUC, Cmax, Tmax), in vitro tools (dissolution testing, IVIVC), advanced sampling and analytical methods (LC-MS/MS, microdialysis), study design elements (crossover, washout), and regulatory bioequivalence criteria. These items are designed to deepen understanding, reinforce principles applied in modern bio-analytical laboratories, and prepare students for exams and research involving bioavailability and bioequivalence assessments.

Q1. What parameter is most directly indicative of the extent of systemic drug exposure after oral administration?

• Maximum plasma concentration (Cmax)
• Time to reach Cmax (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. Which study design is most commonly recommended by regulatory agencies for bioequivalence testing of immediate-release oral products?

• Parallel group design
• Two-period, two-sequence crossover design
• Single-arm open-label study
• Factorial design

Correct Answer: Two-period, two-sequence crossover design

Q3. Absolute bioavailability is defined as:

• The AUC after oral dosing divided by the AUC after intravenous dosing, corrected for dose
• The fraction of a dose absorbed from the gastrointestinal tract only
• The ratio of Cmax of test to reference product
• Time required for 50% of the dose to be eliminated

Correct Answer: The AUC after oral dosing divided by the AUC after intravenous dosing, corrected for dose

Q4. Which analytical technique is considered the gold standard for quantifying drug concentrations in biological matrices for bioavailability studies?

• HPLC with UV detection
• LC-MS/MS (liquid chromatography–tandem mass spectrometry)
• Capillary electrophoresis
• Immunoassay (ELISA)

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

Q5. In non-compartmental analysis, which parameter is used to estimate clearance (CL) after intravenous dosing?

• CL = Dose / AUC
• CL = Vd / t1/2
• CL = AUC / Dose
• CL = Cmax / Tmax

Correct Answer: CL = Dose / AUC

Q6. Which in vitro method is primarily used to predict in vivo dissolution and absorption behavior of oral solid dosage forms?

• Shake flask partition coefficient measurement
• Dissolution testing using USP apparatus
• Polarized light microscopy
• Gel permeation chromatography

Correct Answer: Dissolution testing using USP apparatus

Q7. The 90% confidence interval for the ratio of geometric means of AUC and Cmax between test and reference must generally fall within what range for bioequivalence?

• 70.00%–130.00%
• 90.00%–110.00%
• 80.00%–125.00%
• 50.00%–200.00%

Correct Answer: 80.00%–125.00%

Q8. Deconvolution methods in bioavailability assessment are used to:

• Estimate the fraction of dose absorbed from plasma profiles
• Calculate volume of distribution from terminal slope
• Measure the drug concentration in target tissue directly
• Derive protein binding using ultrafiltration

Correct Answer: Estimate the fraction of dose absorbed from plasma profiles

Q9. Which sampling technique allows continuous monitoring of unbound drug concentrations in interstitial fluid of tissues?

• Venous blood sampling
• Saliva collection
• Microdialysis
• Urine collection

Correct Answer: Microdialysis

Q10. The Wagner–Nelson method is specifically used to:

• Compute absolute bioavailability from oral and IV data
• Estimate the fraction of drug absorbed over time for one-compartment models
• Determine in vitro dissolution rate constants
• Calculate non-compartmental clearance

Correct Answer: Estimate the fraction of drug absorbed over time for one-compartment models

Q11. Which factor most directly impacts Tmax for an orally administered drug?

• Systemic clearance
• Absorption rate constant
• Protein binding in plasma
• Renal excretion rate

Correct Answer: Absorption rate constant

Q12. An IV microdosing study to assess absolute bioavailability uses a sub-pharmacologic IV dose together with an oral therapeutic dose. The primary analytical challenge in such studies is:

• Managing drug–drug interactions between doses
• Measuring extremely low plasma concentrations with high sensitivity
• Ensuring therapeutic effect is not altered
• Maintaining blinded study design

Correct Answer: Measuring extremely low plasma concentrations with high sensitivity

Q13. Which in vitro cell model is commonly used to evaluate intestinal permeability as a surrogate for absorption?

• HepG2 hepatocyte monolayer
• Caco-2 cell monolayer
• CHO cell suspension
• 3T3 fibroblast culture

Correct Answer: Caco-2 cell monolayer

Q14. In a two-period crossover bioequivalence study, an inadequate washout period may primarily cause:

• Increased inter-subject variability but no bias
• Carryover effects leading to biased treatment comparisons
• Improved precision of AUC estimates
• Lower within-subject variability

Correct Answer: Carryover effects leading to biased treatment comparisons

Q15. Which approach provides a direct imaging method to study gastrointestinal transit and site of drug release for oral formulations?

• Gamma scintigraphy
• Magnetic resonance spectroscopy of plasma
• IV bolus pharmacokinetic profiling
• Urinary excretion profiling

Correct Answer: Gamma scintigraphy

Q16. Interpreting bioavailability differences due to high first-pass metabolism is best assessed by comparing:

• Oral AUC to oral Cmax
• Oral AUC to IV AUC corrected for dose
• Urinary excretion to plasma protein binding
• In vitro dissolution to in vitro permeability

Correct Answer: Oral AUC to IV AUC corrected for dose

Q17. Population pharmacokinetic (popPK) analyses help assess bioavailability by:

• Providing individual renal clearance values only
• Estimating typical PK parameters and identifying covariates that affect exposure across a population
• Replacing the need for LC-MS/MS assays
• Eliminating the requirement for crossover designs

Correct Answer: Estimating typical PK parameters and identifying covariates that affect exposure across a population

Q18. A reliable in vitro–in vivo correlation (IVIVC) Level A indicates:

• A single point correlation between dissolution and Cmax
• A point-to-point relationship between in vitro dissolution and in vivo absorption profile
• No predictive relationship between dissolution and absorption
• Only rank-order equivalence between products

Correct Answer: A point-to-point relationship between in vitro dissolution and in vivo absorption profile

Q19. Which statistical transformation is typically applied to AUC and Cmax before bioequivalence analysis?

• Square-root transformation
• No transformation (raw data used)
• Logarithmic transformation
• Reciprocal transformation

Correct Answer: Logarithmic transformation

Q20. When a metabolite is active and contributes significantly to pharmacological effect, bioavailability assessment should:

• Ignore metabolite measurements and focus on parent drug only
• Include quantification of both parent compound and active metabolite in PK analysis
• Use only in vitro assays to predict metabolite exposure
• Apply IVIVC without clinical studies

Correct Answer: Include quantification of both parent compound and active metabolite in PK analysis

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