FPGEE Pharmacokinetics 3 — Questions and Answers
Question 1: A drug undergoes saturable (Michaelis-Menten) hepatic metabolism. Which clinical consequence is most expected when the dose is increased from 200 mg to 300 mg?
- Proportional increase in plasma concentration
- Disproportionately large increase in plasma concentration (Correct answer)
- Decreased half-life due to enzyme induction
- Linear increase in AUC
Correct answer: Disproportionately large increase in plasma concentration
Near saturation, small dose increases cause disproportionately large rises in plasma concentration because elimination capacity is overwhelmed.
Question 2: For a two-compartment model, the initial rapid decline in plasma concentration after IV bolus primarily represents which process?
- Renal elimination
- Distribution into peripheral tissues (alpha phase) (Correct answer)
- Enterohepatic recirculation
- Protein binding equilibration only
Correct answer: Distribution into peripheral tissues (alpha phase)
The alpha (distribution) phase reflects rapid drug transfer from central compartment (plasma) into peripheral tissue compartments.
Question 3: Which equation correctly relates clearance (CL), volume of distribution (Vd), and half-life (t½)?
- t½ = Vd / CL
- t½ = 0.693 × Vd / CL (Correct answer)
- t½ = CL × Vd
- t½ = 0.693 × CL / Vd
Correct answer: t½ = 0.693 × Vd / CL
The correct relationship is t½ = 0.693 × Vd / CL, derived from first-order elimination kinetics.
Question 4: A drug has 95% plasma protein binding. Which statement about free (unbound) drug is most accurate?
- Free drug constitutes 95% of total drug
- Free drug is the pharmacologically active fraction (Correct answer)
- Protein-bound drug crosses membranes freely
- Protein binding has no effect on drug distribution
Correct answer: Free drug is the pharmacologically active fraction
Only free (unbound) drug can cross membranes, interact with receptors, and be pharmacologically active or eliminated.
Question 5: A loading dose is calculated primarily based on which pharmacokinetic parameter?
- Clearance
- Half-life
- Volume of distribution (Correct answer)
- Bioavailability
Correct answer: Volume of distribution
Loading dose = Target Cp × Vd / F; volume of distribution determines how much drug is needed to achieve the desired plasma concentration immediately.
Question 6: Which route of administration completely bypasses first-pass metabolism?
- Oral
- Rectal (proximal)
- Sublingual (Correct answer)
- Buccal mucosa
Correct answer: Sublingual
Sublingual administration drains directly into systemic circulation via lingual and jugular veins, completely bypassing hepatic first-pass metabolism.
Question 7: During hepatic enzyme induction by rifampin, which pharmacokinetic change is most expected for a co-administered drug?
- Increased AUC and prolonged half-life
- Decreased AUC and shortened half-life (Correct answer)
- Increased bioavailability only
- Decreased renal clearance
Correct answer: Decreased AUC and shortened half-life
Enzyme induction increases hepatic metabolism, reducing AUC (less drug exposure) and shortening half-life of co-administered substrates.
FPGEE Pharmacokinetics 3
A drug undergoes saturable (Michaelis-Menten) hepatic metabolism.
Which clinical consequence is most expected when the dose is increased from 200 mg to 300 mg?