Preclinical screening principles: dose selection and conversions MCQs With Answer

Introduction

This quiz-focused blog covers preclinical screening principles specifically on dose selection and interspecies dose conversions — essential topics for M.Pharm students preparing for pharmacology and toxicology roles. You will find clear explanations and targeted multiple-choice questions that reinforce concepts such as NOAEL, MTD, LD50, HED calculation using Km/BSA, allometric scaling, MABEL, MRSD and safety factors. The questions are designed to test applied understanding: converting animal doses to human equivalents, choosing appropriate starting doses for first-in-human studies, and appreciating limitations of simple mg/kg scaling. Use this set to sharpen decision-making for preclinical dose selection and regulatory-relevant calculations.

Q1. What does NOAEL stand for in toxicology studies?

• No Observed Adverse Effect Level — the highest dose at which no adverse effects are observed
• New Observed Adverse Effect Limit — a newly discovered toxic threshold
• Normal Observed Activity and Effect Level — typical observed activity in controls
• Non-Observed Activity Exposure Limit — a minimal exposure limit

Correct Answer: No Observed Adverse Effect Level — the highest dose at which no adverse effects are observed

Q2. What is the Maximum Tolerated Dose (MTD) defined as?

• The lowest dose causing any biological effect
• The dose that causes death in 50% of animals
• The highest dose that does not cause unacceptable toxicity
• The recommended clinical starting dose for humans

Correct Answer: The highest dose that does not cause unacceptable toxicity

Q3. LD50 refers to which of the following?

• Lowest dose producing 50% of maximal therapeutic effect
• Median lethal dose that kills 50% of the test animals
• Lowest detectable dose in a bioassay
• Limit dose used in chronic toxicity studies

Correct Answer: Median lethal dose that kills 50% of the test animals

Q4. Which formula correctly converts an animal dose (mg/kg) to a human equivalent dose (HED, mg/kg) using Km factors?

• HED (mg/kg) = Animal dose (mg/kg) × (Human Km / Animal Km)
• HED (mg/kg) = Animal dose (mg/kg) × (Animal Km / Human Km)
• HED (mg/kg) = Animal dose (mg/kg) ÷ (Animal Km × Human Km)
• HED (mg/kg) = Animal dose (mg/kg) + (Animal Km − Human Km)

Correct Answer: HED (mg/kg) = Animal dose (mg/kg) × (Animal Km / Human Km)

Q5. What is the standard Km value commonly used for an adult human (60 kg) in BSA-based conversions?

• 3
• 6
• 20
• 37

Correct Answer: 37

Q6. Which of the following approximate Km values is used for a mouse?

• 37
• 20
• 6
• 3

Correct Answer: 3

Q7. Convert a mouse dose of 50 mg/kg to HED (mg/kg) using Km(mouse)=3 and Km(human)=37. What is the approximate HED?

• ≈0.74 mg/kg
• ≈4.05 mg/kg
• ≈15.0 mg/kg
• ≈62.3 mg/kg

Correct Answer: ≈4.05 mg/kg

Q8. The Maximum Recommended Starting Dose (MRSD) for first-in-human studies is typically derived by:

• Using the animal LD50 converted to humans without safety factors
• Converting animal NOAEL to HED and dividing by an appropriate safety factor
• Directly applying the highest efficacious animal dose (mg/kg) to humans
• Using only in vitro potency (IC50) values

Correct Answer: Converting animal NOAEL to HED and dividing by an appropriate safety factor

Q9. What does MABEL stand for and why is it used?

• Maximum Anticipated Biological Effect Level — to determine toxic dose limits
• Minimum Anticipated Biological Effect Level — to select very conservative starting doses based on pharmacology
• Median Anticipated Benefit/Efficacy Level — to estimate therapeutic window
• Measured Animal Bioequivalent Level — to compare animal and human exposures

Correct Answer: Minimum Anticipated Biological Effect Level — to select very conservative starting doses based on pharmacology

Q10. Allometric scaling commonly uses which exponent relating physiological parameters to body weight?

• 0.25
• 0.50
• 0.75
• 1.00

Correct Answer: 0.75

Q11. How is the Therapeutic Index (TI) typically calculated?

• ED50 divided by LD50
• LD50 divided by ED50
• NOAEL divided by MTD
• HED divided by animal dose

Correct Answer: LD50 divided by ED50

Q12. For a highly potent biologic with receptor-mediated effects, which approach is generally preferred to select a safe first-in-human dose?

• Use only animal LD50 converted by BSA
• Use the Minimum Anticipated Biological Effect Level (MABEL)
• Use the highest animal efficacious dose directly scaled by mg/kg
• Use historical human doses of small molecules

Correct Answer: Use the Minimum Anticipated Biological Effect Level (MABEL)

Q13. Convert a rat dose of 10 mg/kg to HED (mg/kg) using Km(rat)=6 and Km(human)=37. What is the approximate HED?

• ≈0.62 mg/kg
• ≈1.62 mg/kg
• ≈6.17 mg/kg
• ≈61.7 mg/kg

Correct Answer: ≈1.62 mg/kg

Q14. Which conversion method better accounts for interspecies differences in metabolic rate when scaling doses?

• Simple mg/kg scaling
• Body Surface Area (BSA)-based conversion using Km
• Using only in vitro IC50 values
• Converting by animal age instead of weight

Correct Answer: Body Surface Area (BSA)-based conversion using Km

Q15. Which of the following is LEAST relevant for scientific preclinical dose selection?

• Pharmacokinetic/pharmacodynamic (PK/PD) data
• Repeat-dose toxicology studies including NOAEL
• In vitro potency and target occupancy data
• Market launch price and marketing strategy

Correct Answer: Market launch price and marketing strategy

Q16. A common default safety factor applied when converting animal NOAEL-derived HED to a human starting dose is:

• 2
• 10
• 50
• 1000

Correct Answer: 10

Q17. In the Km approach, what does the Km value represent?

• The ratio of animal metabolic rate to human metabolic rate
• Species-specific factor equal to body weight (kg) divided by body surface area (m²)
• The fixed conversion factor from mg to µg for each species
• The average lifespan-adjusted dose multiplier

Correct Answer: Species-specific factor equal to body weight (kg) divided by body surface area (m²)

Q18. If a dog NOAEL is 10 mg/kg, Km(dog)=20 and Km(human)=37, what is the HED (mg/kg) from this NOAEL?

• ≈1.85 mg/kg
• ≈5.41 mg/kg
• ≈18.5 mg/kg
• ≈54.1 mg/kg

Correct Answer: ≈5.41 mg/kg

Q19. How is the safety margin (or therapeutic margin) commonly defined in preclinical assessment?

• Ratio of ED50 to LD50
• Difference between MRSD and HED
• Ratio of NOAEL (or toxic benchmark) to the intended therapeutic exposure
• Sum of NOAEL and ED50

Correct Answer: Ratio of NOAEL (or toxic benchmark) to the intended therapeutic exposure

Q20. What is a key limitation of simple mg/kg dose scaling when converting animal doses to humans?

• It accurately accounts for metabolic rate differences across species
• It ignores body surface area and metabolic scaling, potentially misestimating exposures
• It is always more conservative than BSA-based methods
• It is the regulatory preferred method for all drug classes

Correct Answer: It ignores body surface area and metabolic scaling, potentially misestimating exposures

Download