Toxicokinetic evaluation in preclinical studies MCQs With Answer

This quiz collection on toxicokinetic evaluation in preclinical studies is designed for M.Pharm students preparing for Modern Bio-Analytical Techniques (MPA 202T). It focuses on the principles and practical considerations of toxicokinetics — absorption, distribution, metabolism, excretion (ADME) — and how these are measured, interpreted and applied during nonclinical safety assessment. Questions cover study design, sampling strategies, analytical techniques, data analysis (non‑compartmental and compartmental), metabolite identification, scaling between species, and TK–TD integration. Each MCQ includes realistic distractors and precise answers to sharpen understanding of both conceptual and technical details essential for designing, conducting, and interpreting toxicokinetic studies in preclinical development.

Q1. What is the primary objective of toxicokinetic studies in preclinical safety assessment?

• To determine the maximum tolerated dose in humans
• To characterize absorption, distribution, metabolism and excretion (ADME) and systemic exposure of the test article
• To evaluate pharmacodynamic endpoint responses only
• To replace toxicology studies by measuring in vitro stability

Correct Answer: To characterize absorption, distribution, metabolism and excretion (ADME) and systemic exposure of the test article

Q2. Which pharmacokinetic parameter is considered model‑independent and is commonly estimated by non‑compartmental analysis?

• Apparent volume of distribution (Vd)
• Total body clearance (CL)
• Area under the plasma concentration–time curve (AUC)
• Terminal half‑life (t1/2) estimated from a compartment model

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

Q3. How is absolute oral bioavailability (F) calculated from plasma AUC measurements?

• F = (AUCiv / AUCpo) × (Dosepo / Doseiv)
• F = (Cmax,po / Cmax,iv) × 100
• F = (AUCpo × Doseiv) / (AUCiv × Dosepo)
• F = CLpo / CLiv

Correct Answer: F = (AUCpo × Doseiv) / (AUCiv × Dosepo)

Q4. In allometric scaling of clearance across mammalian species, which exponent is most commonly used as a starting point?

• 0.25
• 0.50
• 0.75
• 1.00

Correct Answer: 0.75

Q5. When is whole blood typically preferred over plasma as the sampling matrix in toxicokinetic studies?

• When the analyte undergoes extensive plasma esterase hydrolysis in vitro
• When the compound shows high erythrocyte partitioning (blood‑to‑plasma ratio >1)
• When only unbound concentrations are required
• When sample volume is unlimited and simple centrifugation is desired

Correct Answer: When the compound shows high erythrocyte partitioning (blood‑to‑plasma ratio >1)

Q6. Which statement best describes the pharmacokinetic relevance of plasma protein binding?

• Highly protein-bound drugs have faster renal clearance than unbound drugs
• Only the unbound fraction is available for metabolism, excretion and pharmacologic/toxicologic effect
• Protein binding determines the absolute oral bioavailability directly
• Protein binding is irrelevant for tissue distribution

Correct Answer: Only the unbound fraction is available for metabolism, excretion and pharmacologic/toxicologic effect

Q7. What does LLOQ (Lower Limit of Quantification) signify in an analytical method for TK studies?

• The lowest concentration that can be detected but not quantified
• The lowest concentration that can be quantitatively measured with acceptable precision and accuracy
• The highest concentration that can be reliably measured
• The concentration corresponding to the limit of detection (LOD)

Correct Answer: The lowest concentration that can be quantitatively measured with acceptable precision and accuracy

Q8. What is a primary advantage of microsampling techniques (e.g., DBS or capillary microsamples) in rodent toxicokinetic studies?

• They eliminate the need for bioanalytical method validation
• They enable serial sampling from the same animal, reducing group sizes and inter‑animal variability
• They provide higher absolute accuracy than venous plasma sampling for all compounds
• They always simplify metabolite identification workflows

Correct Answer: They enable serial sampling from the same animal, reducing group sizes and inter‑animal variability

Q9. Which concentration–time profile pattern is a classic indicator of enterohepatic recirculation?

• A monoexponential decline with a single terminal slope
• Rapid absorption with very short half‑life and no secondary peaks
• Multiple peaks or a secondary rising phase in the plasma concentration–time curve
• Flat concentration–time profile with no discernible elimination

Correct Answer: Multiple peaks or a secondary rising phase in the plasma concentration–time curve

Q10. Which relationship correctly links terminal half‑life (t1/2), apparent volume of distribution (Vd) and clearance (CL)?

• t1/2 = CL / (0.693 × Vd)
• t1/2 = 0.693 × Vd / CL
• t1/2 = Vd × CL
• t1/2 = 0.5 × CL / Vd

Correct Answer: t1/2 = 0.693 × Vd / CL

Q11. Approximately how many half‑lives are required to reach steady state during continuous dosing?

• 1 half‑life
• 2 half‑lives
• 4–5 half‑lives
• 10–12 half‑lives

Correct Answer: 4–5 half‑lives

Q12. Which formula gives the accumulation ratio (R) for a drug dosed at regular intervals (tau) assuming first‑order elimination?

• R = 1 − e^(−k × tau)
• R = 1 / (1 − e^(−k × tau))
• R = e^(k × tau)
• R = (CL × tau) / Vd

Correct Answer: R = 1 / (1 − e^(−k × tau))

Q13. Which analytical approach is most appropriate for structural elucidation and profiling of low‑level metabolites in preclinical TK studies?

• Immunoassay screening only
• High‑resolution mass spectrometry with LC separation and MS/MS fragmentation (LC‑HRMS/MS)
• Single‑quadrupole UV detection without MS
• Colorimetric total radioactivity measurement only

Correct Answer: High‑resolution mass spectrometry with LC separation and MS/MS fragmentation (LC‑HRMS/MS)

Q14. What is the main purpose of whole‑body radiolabeled mass balance studies (e.g., 14C) in TK assessment?

• To replace LC‑MS methods for quantitative plasma assays
• To evaluate protein binding in plasma
• To determine excretion pathways, total recovery and metabolite distribution (mass balance)
• To directly measure unbound interstitial concentrations

Correct Answer: To determine excretion pathways, total recovery and metabolite distribution (mass balance)

Q15. Which observation is most indicative of non‑linear (saturable) toxicokinetics?

• AUC increases proportionally with dose across the tested range
• Cmax decreases despite increasing dose
• A disproportionate (more than dose‑proportional) increase in AUC with increasing dose due to saturation of clearance
• Terminal half‑life remains constant regardless of dose

Correct Answer: A disproportionate (more than dose‑proportional) increase in AUC with increasing dose due to saturation of clearance

Q16. Which modelling approach is used to quantitatively link internal exposure to observed toxicological responses in preclinical studies?

• Compartmental PK modelling without effect linkage
• PK/PD (toxicokinetic–toxicodynamic) modelling connecting exposure to effect
• Only empirical dose–response curves with no exposure data
• Population genetics modelling

Correct Answer: PK/PD (toxicokinetic–toxicodynamic) modelling connecting exposure to effect

Q17. Regulatory guidance typically recommends performing toxicokinetic assessments in which species during nonclinical toxicity programs?

• Only a single rodent species for small molecules
• One rodent and one non‑rodent species to capture interspecies metabolic differences
• Only non‑human primates for all compounds
• Only in vitro human hepatocytes are required

Correct Answer: One rodent and one non‑rodent species to capture interspecies metabolic differences

Q18. Which hepatic clearance model explicitly uses hepatic blood flow (Qh), intrinsic clearance (CLint) and fraction unbound (fu) to predict hepatic clearance?

• Parallel tube model
• Well‑stirred (venous equilibrium) model
• First‑order absorption model
• Two‑compartment peripheral model

Correct Answer: Well‑stirred (venous equilibrium) model

Q19. How does enzyme induction by a concomitant xenobiotic typically affect the toxicokinetics of a substrate drug?

• Increased AUC and increased half‑life of the substrate
• No change in clearance or exposure
• Reduced systemic exposure due to increased metabolic clearance (lower AUC)
• Immediate precipitation of the drug in plasma

Correct Answer: Reduced systemic exposure due to increased metabolic clearance (lower AUC)

Q20. What is the primary advantage of microdialysis in preclinical tissue toxicokinetic studies?

• It measures total tissue concentration including bound drug
• It directly measures intracellular drug concentrations across membranes
• It samples and measures unbound drug concentrations in the interstitial fluid, reflecting pharmacologically available tissue exposure
• It is suitable only for measuring large biologics that do not cross membranes

Correct Answer: It samples and measures unbound drug concentrations in the interstitial fluid, reflecting pharmacologically available tissue exposure

Download