MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 4 — Questions and Answers
Question 1: Which of the following best explains why phenytoin exhibits zero-order kinetics at therapeutic doses?
- It has a very large volume of distribution
- Its metabolizing enzymes become saturated within the therapeutic range (Correct answer)
- It undergoes extensive enterohepatic recirculation
- It is predominantly eliminated by the kidneys unchanged
Correct answer: Its metabolizing enzymes become saturated within the therapeutic range
Phenytoin saturates CYP2C9/CYP2C19 at therapeutic concentrations, so a constant amount (not fraction) is metabolized per unit time — zero-order kinetics.
Question 2: In the context of pharmacodynamics, receptor reserve (spare receptors) means that:
- Only a fraction of total receptors need to be occupied to produce a maximum response (Correct answer)
- Receptors are synthesized in excess and stored for later use
- Unoccupied receptors have constitutive activity
- Maximum response requires >90% receptor occupancy
Correct answer: Only a fraction of total receptors need to be occupied to produce a maximum response
Receptor reserve exists when a maximum biological response can be achieved by occupying only a small fraction of the total available receptors.
Question 3: When two drugs are given together and their combined effect is greater than additive, this interaction is termed:
- Antagonism
- Synergism (Correct answer)
- Potentiation
- Infra-additive
Correct answer: Synergism
Synergism (or superadditivity) occurs when the combined drug effect exceeds the simple sum of individual effects.
Question 4: The bioequivalence of two formulations is assessed primarily by comparing:
- Their receptor binding affinities in vitro
- AUC and Cmax under standardized conditions (Correct answer)
- Volume of distribution and protein binding
- LD50 values in animal models
Correct answer: AUC and Cmax under standardized conditions
Bioequivalence studies compare AUC (total exposure) and Cmax (peak concentration) between test and reference formulations within 80–125% confidence intervals.
Question 5: A drug has a hepatic extraction ratio of 0.9. Its oral bioavailability is primarily limited by:
- Incomplete dissolution in the GI tract
- Extensive first-pass hepatic metabolism (Correct answer)
- Poor membrane permeability
- High renal clearance
Correct answer: Extensive first-pass hepatic metabolism
A high extraction ratio (0.9) means 90% of absorbed drug is removed by the liver on first pass, severely limiting systemic bioavailability.
Question 6: Which pharmacokinetic model assumes that the body behaves as a single homogeneous compartment for drug distribution?
- Two-compartment open model
- Physiologically-based pharmacokinetic (PBPK) model
- One-compartment open model (Correct answer)
- Multi-exponential disposition model
Correct answer: One-compartment open model
The one-compartment model assumes instantaneous and uniform drug distribution throughout the body, with log-linear decline in plasma concentration.
Question 7: Upregulation of receptors typically occurs in response to:
- Prolonged exposure to high concentrations of agonist
- Chronic antagonist blockade or denervation (Correct answer)
- Repeated administration of partial agonists
- Acute administration of a full agonist
Correct answer: Chronic antagonist blockade or denervation
Prolonged antagonist administration or denervation deprives receptors of stimulation, triggering compensatory upregulation and increased receptor density.
MPharm Master of Pharmacy Master of Pharmacy: Pharmacokinetics and Pharmacodynamics 4
Which of the following best explains why phenytoin exhibits zero-order kinetics at therapeutic doses?