Introduction to clinical pharmacokinetics: non-compartmental models MCQs With Answer

Introduction:
This quiz set on Introduction to Clinical Pharmacokinetics: Non-Compartmental Models is designed for M.Pharm students to reinforce core principles of non-compartmental analysis (NCA). Non-compartmental models provide model-independent methods to estimate exposure (AUC), elimination rates, clearance, volume of distribution, mean residence time and bioavailability directly from plasma concentration–time data. The questions focus on practical computation concepts — trapezoidal rules, terminal slope estimation, extrapolated AUC, and interpretation of NCA parameters — plus common pitfalls in dataset handling and regulatory considerations. Working through these MCQs will strengthen your ability to perform and critically evaluate NCA in clinical pharmacokinetic studies.

Q1. What does the AUC0–∞ represent in non-compartmental analysis?

• The peak plasma concentration achieved after dosing
• The total drug exposure from time zero extrapolated to infinity
• The clearance normalized by dose
• The time to reach steady state

Correct Answer: The total drug exposure from time zero extrapolated to infinity

Q2. Which method is commonly used to calculate AUC from observed concentration–time data in NCA?

• Simpson’s rule
• Trapezoidal rule
• Gaussian quadrature
• Laplace transform

Correct Answer: Trapezoidal rule

Q3. How is the terminal elimination rate constant (λz) typically estimated in non-compartmental analysis?

• By linear regression of log-concentration versus time in the terminal phase
• By dividing Cmax by AUC
• By integrating concentration over time
• By calculating the area under the first moment curve

Correct Answer: By linear regression of log-concentration versus time in the terminal phase

Q4. Mean residence time (MRT) in NCA is calculated as:

• MRT = AUC0–∞ / Dose
• MRT = AUMC0–∞ / AUC0–∞
• MRT = Dose / Clearance
• MRT = ln(2) / λz

Correct Answer: MRT = AUMC0–∞ / AUC0–∞

Q5. In non-compartmental estimation of clearance (CL/F) after oral dosing, which expression is correct?

• CL/F = Dose / AUC0–∞
• CL/F = AUC0–∞ / Dose
• CL/F = Vz × λz
• CL/F = ln(2) / t1/2

Correct Answer: CL/F = Dose / AUC0–∞

Q6. Volume of distribution during terminal phase (Vz/F) in NCA is calculated as:

• Vz/F = CL/F × MRT
• Vz/F = (CL/F) / λz
• Vz/F = Dose / Cmax
• Vz/F = AUC / AUMC

Correct Answer: Vz/F = (CL/F) / λz

Q7. Which trapezoidal method is preferred when concentrations change exponentially between sampling points?

• Linear trapezoidal rule
• Log-linear trapezoidal rule
• Simpson’s rule
• Rectangular rule

Correct Answer: Log-linear trapezoidal rule

Q8. What is the primary reason for extrapolating AUC to infinity (AUCext) and evaluating percent extrapolated AUC?

• To estimate Cmax more accurately
• To determine safety margins for toxicology studies
• To assess the reliability of total exposure estimation
• To calculate the absorption rate constant (ka)

Correct Answer: To assess the reliability of total exposure estimation

Q9. Which criterion is commonly used to judge acceptability of AUC extrapolation?

• %AUC extrapolated should be less than 20%
• %AUC extrapolated should be greater than 50%
• %AUC extrapolated should equal 100%
• %AUC extrapolated should be negative

Correct Answer: %AUC extrapolated should be less than 20%

Q10. When selecting points for terminal slope estimation, which feature is most important?

• Using the earliest post-dose samples only
• Choosing points that visually form a straight line on semilog plot
• Including the Cmax point always
• Using only non-detectable concentrations

Correct Answer: Choosing points that visually form a straight line on semilog plot

Q11. AUMC is the area under the first moment curve. What additional information does AUMC provide compared to AUC?

• Rate of absorption
• First-pass metabolism
• Time-weighted exposure information used to compute MRT
• Volume of distribution directly

Correct Answer: Time-weighted exposure information used to compute MRT

Q12. In NCA, why might a log-linear trapezoidal rule be applied for descending concentrations but linear for ascending?

• Because ascending concentrations are always linear in time
• Because exponential decline approximates better with log-linear integration while absorption phase is often linear between points
• Because log-linear requires fewer sampling points
• Because regulatory guidance mandates mixed rules

Correct Answer: Because exponential decline approximates better with log-linear integration while absorption phase is often linear between points

Q13. Which of the following is a limitation of non-compartmental analysis?

• It requires a predefined compartmental model
• It cannot estimate parameters like clearance or volume
• It provides less mechanistic insight into absorption and distribution processes
• It always overestimates AUC

Correct Answer: It provides less mechanistic insight into absorption and distribution processes

Q14. What is the implication of a poorly characterized terminal phase (e.g., few samples, noisy data) for NCA?

• λz will be estimated with high precision
• MRT becomes independent of λz
• Estimates of AUC0–∞, t1/2, and derived clearance/volume may be unreliable
• Cmax measurement improves

Correct Answer: Estimates of AUC0–∞, t1/2, and derived clearance/volume may be unreliable

Q15. If the last measurable concentration is CLAST and λz is known, how is the extrapolated AUC (AUClast–∞) computed?

• AUClast–∞ = CLAST × λz
• AUClast–∞ = CLAST / λz
• AUClast–∞ = λz / CLAST
• AUClast–∞ = CLAST × Dose

Correct Answer: AUClast–∞ = CLAST / λz

Q16. For an intravenous bolus dose in NCA, what is the relationship between CL and AUC?

• CL = Dose × AUC
• CL = Dose / AUC
• CL = AUC / Dose
• CL = Vz × λz

Correct Answer: CL = Dose / AUC

Q17. Which data processing step is essential before performing NCA on clinical data?

• Converting concentrations to logarithms for all computations
• Imputing zero concentrations as negative values
• Flagging and handling below limit of quantification (BLQ) values appropriately
• Normalizing all concentrations to Cmax

Correct Answer: Flagging and handling below limit of quantification (BLQ) values appropriately

Q18. In a crossover bioequivalence study, which NCA parameter is most commonly used to compare overall exposure between formulations?

• Cmax only
• AUC0–t and AUC0–∞
• λz only
• MRT only

Correct Answer: AUC0–t and AUC0–∞

Q19. What is the practical consequence if %AUC extrapolated is high (e.g., >30%) in a pharmacokinetic study?

• Total exposure is precisely estimated
• Regulatory acceptance is guaranteed
• Reliability of AUC0–∞ is questionable and additional sampling or study redesign may be needed
• Clearance estimates are unaffected

Correct Answer: Reliability of AUC0–∞ is questionable and additional sampling or study redesign may be needed

Q20. Which statement best distinguishes non-compartmental analysis from compartmental modeling?

• NCA requires fewer assumptions about the number and linkage of compartments and focuses on observed data summaries, while compartmental modeling fits a mechanistic model to describe kinetics
• NCA always provides parameter estimates with mechanistic interpretation while compartmental models do not
• Compartmental models cannot predict concentrations, whereas NCA can
• NCA is only applicable to intravenous dosing and never to oral dosing

Correct Answer: NCA requires fewer assumptions about the number and linkage of compartments and focuses on observed data summaries, while compartmental modeling fits a mechanistic model to describe kinetics

Download