Estimation and determinants of bioavailability MCQs With Answer

Introduction: This collection of MCQs on estimation and determinants of bioavailability is designed specifically for M.Pharm students preparing for advanced topics in Clinical Pharmacokinetics and Therapeutic Drug Monitoring. The questions cover fundamental principles, calculation-based problems, experimental approaches, and physiological and formulation factors that influence systemic drug availability. Emphasis is placed on methods to estimate absolute and relative bioavailability (AUC-based, urinary recovery, isotopic techniques), critical assumptions in study design, and practical factors such as first-pass metabolism, transporters, food effects, and kinetics phenomena like flip‑flop. Use these questions to test conceptual understanding and calculation skills necessary for designing and interpreting bioavailability and bioequivalence studies.

Q1. What is the correct formula for absolute bioavailability (F) using AUC measurements after oral and intravenous administration?

• F = (AUCpo * Doseiv) / (AUCiv * Dosepo)
• F = (AUCiv * Dosepo) / (AUCpo * Doseiv)
• F = (AUCpo / Dosepo) + (AUCiv / Doseiv)
• F = (AUCpo * AUCiv) / (Dosepo * Doseiv)

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

Q2. Relative bioavailability between a test and reference oral product is most commonly assessed by comparing which pharmacokinetic parameter?

• Clearance (CL)
• Area under the plasma concentration–time curve (AUC)
• Volume of distribution (Vd)
• Elimination half‑life (t1/2)

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

Q3. Which set of factors collectively determines the oral bioavailability of a drug?

• Only chemical stability in acidic media and membrane permeability
• Solubility, gastrointestinal stability, permeability, first‑pass metabolism, and efflux transporters
• Renal clearance and protein binding exclusively
• Manufacturing batch size and color of tablet

Correct Answer: Solubility, gastrointestinal stability, permeability, first‑pass metabolism, and efflux transporters

Q4. If an intravenous formulation is unavailable, which approach can be used to estimate systemic availability provided the drug is significantly excreted unchanged in urine?

• Use population pharmacokinetic modeling without any IV data
• Compare urinary recovery of unchanged drug after oral dose with urinary recovery after an oral reference dose
• Use urinary excretion of unchanged drug after oral dose and compare to urinary recovery after an IV microdose or literature IV data
• Estimate bioavailability from Cmax alone

Correct Answer: Use urinary excretion of unchanged drug after oral dose and compare to urinary recovery after an IV microdose or literature IV data

Q5. The hepatic first‑pass extraction (Eh) modifies oral bioavailability according to which relationship (assuming fraction absorbed Fa and fraction escaping gut metabolism Fg)?

• F = Fa × (1 + Eh) × Fg
• F = Fa × Fg × (1 − Eh)
• F = Fa / (Fg × Eh)
• F = Fa + Fg + Eh

Correct Answer: F = Fa × Fg × (1 − Eh)

Q6. Which equation correctly relates AUC to dose, bioavailability (F), and clearance (CL) after an extravascular dose?

• AUC = CL / (Dose × F)
• AUC = Dose × F / CL
• AUC = Dose / (CL × F)
• AUC = Dose × CL / F

Correct Answer: AUC = Dose × F / CL

Q7. Why do intramuscular (IM) and subcutaneous (SC) routes often show higher systemic availability than oral administration?

• They undergo extensive first‑pass hepatic metabolism making them less bioavailable
• They bypass intestinal and hepatic first‑pass metabolism, reducing presystemic loss
• They always produce a longer half‑life, increasing bioavailability
• They increase renal clearance, raising systemic exposure

Correct Answer: They bypass intestinal and hepatic first‑pass metabolism, reducing presystemic loss

Q8. Which clinical study design is most appropriate for comparing bioavailability between two oral formulations in healthy volunteers?

• Parallel group design without randomization
• Randomized two‑period crossover with adequate washout
• Single‑dose open‑label administration of both products simultaneously
• Randomized withdrawal study

Correct Answer: Randomized two‑period crossover with adequate washout

Q9. Flip‑flop kinetics in oral pharmacokinetics refers to which situation?

• Elimination rate is much faster than absorption rate so terminal slope reflects absorption
• Absorption is instantaneous and elimination is very slow
• Drug displays non‑linear Michaelis‑Menten elimination only at high dose
• There is alternation between hepatic and renal clearance mechanisms

Correct Answer: Elimination rate is much faster than absorption rate so terminal slope reflects absorption

Q10. Deconvolution analysis in bioavailability assessment is primarily used to:

• Estimate clearance directly from urine data
• Determine the input (absorption) rate profile from observed concentration–time data using a known IV disposition function
• Calculate protein binding from plasma concentrations
• Replace the need for AUC measurements by using Tmax only

Correct Answer: Determine the input (absorption) rate profile from observed concentration–time data using a known IV disposition function

Q11. For a crossover bioavailability study, the washout period should typically be at least:

• 1 half‑life of the drug
• 2 half‑lives of the drug
• 5 half‑lives of the drug
• Not dependent on half‑life; 24 hours is sufficient

Correct Answer: 5 half‑lives of the drug

Q12. How does high plasma protein binding generally affect the absolute bioavailability of an orally administered drug?

• It always increases bioavailability because bound drug is protected from metabolism
• It does not directly change the fraction absorbed (F) but influences distribution and apparent volume of distribution
• It converts first‑order elimination to zero‑order elimination and increases F
• It ensures 100% bioavailability for all drugs

Correct Answer: It does not directly change the fraction absorbed (F) but influences distribution and apparent volume of distribution

Q13. Intestinal P‑glycoprotein (P‑gp) affects oral bioavailability primarily by:

• Enhancing passive diffusion across enterocytes
• Pumping absorbed drug from enterocytes back into the intestinal lumen, reducing net absorption
• Increasing hepatic extraction ratio directly
• Blocking renal tubular secretion to raise plasma levels

Correct Answer: Pumping absorbed drug from enterocytes back into the intestinal lumen, reducing net absorption

Q14. Regulatory acceptance criteria for bioequivalence with respect to AUC require that the 90% confidence interval for the geometric mean ratio (test/reference) falls within:

• 50–150%
• 80–125%
• 90–110%
• 70–130%

Correct Answer: 80–125%

Q15. A sensitive and modern method to estimate absolute bioavailability without administering therapeutic IV doses is:

• Use of a stable isotope‑labeled IV microdose given concurrently with an oral dose and measuring labeled vs unlabeled AUCs
• Estimating from Cmax alone after oral dosing
• Measuring only urinary pH changes after oral dosing
• Assuming 100% absorption for all small molecules

Correct Answer: Use of a stable isotope‑labeled IV microdose given concurrently with an oral dose and measuring labeled vs unlabeled AUCs

Q16. Which property of a drug will most likely reduce its oral bioavailability due to degradation before absorption?

• High lipophilicity
• Acid lability in the stomach
• High hepatic clearance only after absorption
• Extensive protein binding in plasma

Correct Answer: Acid lability in the stomach

Q17. Calculate the absolute bioavailability: AUCpo = 50 mg·h/L after a 100 mg oral dose; AUCiv = 40 mg·h/L after a 20 mg IV dose. What is F?

• 25%
• 50%
• 20%
• 40%

Correct Answer: 25%

Q18. Which physiological change would most likely increase Tmax (time to reach peak concentration) after oral dosing?

• Faster gastric emptying
• Increased intestinal motility
• Slower gastric emptying
• Administration with a clear liquid that speeds transit

Correct Answer: Slower gastric emptying

Q19. Which expression correctly represents the overall fraction of an orally administered dose that reaches systemic circulation (bioavailability)?

• F = Fa × Fg × Fh (where Fa = fraction absorbed, Fg = fraction escaping gut, Fh = fraction escaping hepatic metabolism)
• F = Fa + Fg + Fh
• F = Fa / (Fg × Fh)
• F = (Fa × Fg) − Fh

Correct Answer: F = Fa × Fg × Fh (where Fa = fraction absorbed, Fg = fraction escaping gut, Fh = fraction escaping hepatic metabolism)

Q20. The urinary excretion method to estimate bioavailability relies on which key assumption?

• The drug is completely metabolized before renal excretion
• Renal excretion of unchanged drug is proportional to systemic exposure and collection is complete under linear kinetics
• The drug follows non‑linear elimination kinetics and is only secreted actively
• Plasma protein binding determines urinary recovery exclusively

Correct Answer: Renal excretion of unchanged drug is proportional to systemic exposure and collection is complete under linear kinetics

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