Pharmacokinetics of drug interactions: principles MCQs With Answer

Introduction

This collection of multiple-choice questions focuses on the pharmacokinetics of drug interactions, designed specifically for M.Pharm students preparing for advanced clinical pharmacokinetics and therapeutic drug monitoring exams. Questions cover absorption, distribution, metabolism, excretion, transporter-mediated effects, enzyme induction and inhibition, time-course of interactions, pharmacogenetic influences, and interpretation of changes in pharmacokinetic parameters such as clearance, half-life, and AUC. Emphasis is placed on mechanistic understanding, clinical significance, and how therapeutic drug monitoring and in vitro–in vivo extrapolation inform safe dosing decisions. Use these MCQs to test and deepen your ability to predict, assess, and manage clinically relevant pharmacokinetic drug interactions.

Q1. Which of the following best defines a pharmacokinetic drug interaction?

• An interaction in which one drug changes the plasma concentration of another by altering absorption, distribution, metabolism, or excretion
• An interaction where two drugs have additive pharmacological effects at the same receptor
• An interaction where a drug causes organ toxicity independent of plasma concentration changes
• An interaction only observed during intravenous administration

Correct Answer: An interaction in which one drug changes the plasma concentration of another by altering absorption, distribution, metabolism, or excretion

Q2. Co-administration of oral tetracycline and antacid containing aluminum reduces tetracycline efficacy primarily by which mechanism?

• Induction of hepatic metabolizing enzymes
• Chelation in the gastrointestinal tract reducing absorption
• Competitive inhibition of renal tubular secretion
• Displacement from plasma proteins increasing free fraction

Correct Answer: Chelation in the gastrointestinal tract reducing absorption

Q3. A highly protein-bound drug (99%) is displaced by another drug that binds to the same albumin site. Which statement about total and free concentrations is correct immediately after displacement?

• Total concentration rises while free concentration remains unchanged
• Total concentration falls and free concentration increases proportionally
• Total concentration decreases slightly but free concentration increases substantially
• Neither total nor free concentrations change because clearance compensates instantly

Correct Answer: Total concentration decreases slightly but free concentration increases substantially

Q4. Competitive inhibition of a CYP450 enzyme by Drug A on Drug B typically results in which immediate change to Drug B’s metabolic kinetics?

• Increase in Vmax with no change in Km
• Increase in Km with no change in Vmax
• Decrease in both Km and Vmax
• Irreversible loss of enzyme leading to progressive inhibition

Correct Answer: Increase in Km with no change in Vmax

Q5. Which of the following best describes mechanism-based (time-dependent) inhibition of a drug-metabolizing enzyme?

• Rapid reversible binding that is competitive with the substrate
• Irreversible inactivation of the enzyme after metabolic activation of the inhibitor
• Non-competitive reversible inhibition that increases Vmax
• Enzyme induction via increased gene transcription

Correct Answer: Irreversible inactivation of the enzyme after metabolic activation of the inhibitor

Q6. Chronic rifampin therapy reduces plasma concentrations of many drugs primarily by which mechanism?

• Inhibition of renal tubular reabsorption
• Induction of hepatic CYP enzymes and drug transporters
• Competitive displacement from plasma proteins
• Direct chemical inactivation in the gut lumen

Correct Answer: Induction of hepatic CYP enzymes and drug transporters

Q7. A drug’s oral bioavailability is primarily reduced by a co-administered agent that increases first-pass metabolism. Which parameter most directly decreases?

• Renal clearance
• Apparent volume of distribution (Vd)
• Area under the plasma concentration–time curve (AUC)
• Protein binding percentage

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

Q8. P-glycoprotein (P-gp) inhibition in the intestinal epithelium will most likely cause which effect on an oral P-gp substrate?

• Decreased systemic exposure due to increased efflux
• Increased oral bioavailability due to reduced efflux back into the lumen
• No change because P-gp does not affect pharmacokinetics
• Immediate renal excretion via increased glomerular filtration

Correct Answer: Increased oral bioavailability due to reduced efflux back into the lumen

Q9. Probenecid increases plasma concentrations of penicillin primarily by which pharmacokinetic mechanism?

• Induction of CYP enzymes metabolizing penicillin
• Inhibition of renal tubular secretion of penicillin
• Enhanced gastrointestinal absorption via pH change
• Displacement from plasma proteins causing higher free fraction

Correct Answer: Inhibition of renal tubular secretion of penicillin

Q10. Which parameter is directly proportional to the extent of systemic exposure and is commonly used to quantify the magnitude of a drug interaction?

• Half-life (t1/2)
• Apparent volume of distribution (Vd)
• Area under the curve (AUC)
• Peak urinary excretion rate

Correct Answer: Area under the curve (AUC)

Q11. A strong CYP3A4 inhibitor doubles the AUC of a narrow therapeutic index drug metabolized by CYP3A4. Clinically the most appropriate action is which?

• Continue current dosing; no monitoring needed because total concentration doubles
• Reduce dose of the narrow therapeutic index drug and increase therapeutic drug monitoring frequency
• Add another CYP3A4 substrate to balance the interaction
• Switch to intravenous route to avoid interaction

Correct Answer: Reduce dose of the narrow therapeutic index drug and increase therapeutic drug monitoring frequency

Q12. In a patient who is a CYP2D6 poor metabolizer, which effect is expected when giving a standard dose of a CYP2D6-prodrug requiring bioactivation?

• Increased formation of active metabolite and toxicity
• Reduced formation of active metabolite and decreased therapeutic effect
• No change because prodrugs are not affected by CYP status
• Accelerated renal clearance of parent drug

Correct Answer: Reduced formation of active metabolite and decreased therapeutic effect

Q13. Which of the following best characterizes the time course for enzyme induction compared with reversible enzyme inhibition?

• Induction is rapid (minutes), inhibition is slow (weeks)
• Both induction and inhibition occur immediately after the first dose
• Induction develops over days to weeks; reversible inhibition occurs rapidly after dosing
• Both phenomena are irreversible and persist after drug discontinuation

Correct Answer: Induction develops over days to weeks; reversible inhibition occurs rapidly after dosing

Q14. An investigator uses the ratio AUCR (AUC with inhibitor / AUC without inhibitor). An AUCR of 0.5 indicates what change?

• A twofold increase in exposure
• Half the exposure compared with control (50% reduction)
• No change in exposure
• Exposure is four times greater

Correct Answer: Half the exposure compared with control (50% reduction)

Q15. Which in vitro parameter is most commonly used with inhibitor concentration to predict clinical CYP-mediated drug interactions?

• Protein binding percentage
• Intrinsic clearance (Clint)
• Ki (inhibition constant) or IC50
• Volume of distribution

Correct Answer: Ki (inhibition constant) or IC50

Q16. Antibiotic therapy that eradicates gut bacteria can reduce enterohepatic recirculation of certain drugs. The expected PK effect is typically which?

• Increased AUC due to reduced metabolism by gut flora
• Decreased AUC due to loss of reabsorbed active drug fraction
• No change because enterohepatic recirculation rarely affects exposure
• Immediate increase in renal clearance only

Correct Answer: Decreased AUC due to loss of reabsorbed active drug fraction

Q17. Which interaction is an example of a pharmacodynamic interaction rather than pharmacokinetic?

• Ketoconazole increases midazolam AUC by inhibiting CYP3A4
• Warfarin and aspirin increase bleeding risk through additive antithrombotic effects
• Probenecid reduces renal clearance of penicillin
• Rifampin induces metabolism of oral contraceptives reducing their plasma levels

Correct Answer: Warfarin and aspirin increase bleeding risk through additive antithrombotic effects

Q18. Therapeutic drug monitoring (TDM) is most valuable for assessing drug interactions when which of the following is true?

• The drug has a wide therapeutic index and variable absorption
• The drug has a narrow therapeutic index and measurable concentration-efficacy or concentration-toxicity relationship
• The drug is exclusively renally excreted with no metabolism
• The drug is only given as a single dose

Correct Answer: The drug has a narrow therapeutic index and measurable concentration-efficacy or concentration-toxicity relationship

Q19. Which renal interaction mechanism explains why cimetidine can increase plasma levels of drugs that are secreted in the proximal tubule?

• Competition for glomerular filtration
• Inhibition of renal organic cation/anion transporters reducing tubular secretion
• Enhanced tubular reabsorption due to urine alkalinization
• Induction of renal drug-metabolizing enzymes

Correct Answer: Inhibition of renal organic cation/anion transporters reducing tubular secretion

Q20. A mechanism-based CYP inhibitor produces prolonged interaction after the inhibitor is stopped. The primary reason for persistence is which?

• The inhibitor remains at high plasma levels for months
• Irreversible enzyme inactivation requiring synthesis of new enzyme to restore activity
• Upregulation of transporter proteins prolonging exposure
• Reversible binding that slowly dissociates over hours

Correct Answer: Irreversible enzyme inactivation requiring synthesis of new enzyme to restore activity

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