Introduction: Understanding drug interactions in pharmacokinetics is essential for B.Pharm students preparing for clinical practice and exams. This topic covers how absorption, distribution, metabolism, and excretion (ADME) influence drug-drug interactions, including mechanisms such as CYP450 enzyme induction or inhibition, P-glycoprotein transport, plasma protein displacement, and effects on renal clearance and bioavailability. Recognizing common perpetrators—rifampin, ketoconazole, grapefruit juice, probenecid, and St. John’s wort—and interpreting changes in AUC, clearance, and half-life help predict clinically significant outcomes. Mastery of pharmacokinetic interactions improves safe prescribing and therapeutic monitoring. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary pharmacokinetic mechanism by which rifampin reduces plasma concentrations of many co-administered drugs?
- Inhibition of renal tubular secretion
- Induction of CYP450 enzymes
- Competitive plasma protein displacement
- Blocking intestinal absorption by chelation
Correct Answer: Induction of CYP450 enzymes
Q2. Which change in pharmacokinetic parameter most directly indicates decreased systemic exposure to a drug?
- Increased half-life (t1/2)
- Increased volume of distribution (Vd)
- Decreased area under the curve (AUC)
- Decreased renal clearance (CLr)
Correct Answer: Decreased area under the curve (AUC)
Q3. Grapefruit juice commonly increases plasma levels of certain drugs by which mechanism?
- Induction of intestinal CYP3A4
- Inhibition of intestinal CYP3A4
- Enhancement of renal excretion via OATs
- Increasing gastric pH to improve absorption
Correct Answer: Inhibition of intestinal CYP3A4
Q4. Probenecid increases plasma concentrations of penicillin primarily by:
- Inhibiting renal tubular secretion
- Inducing hepatic metabolism
- Competing for plasma protein binding
- Enhancing gastrointestinal absorption
Correct Answer: Inhibiting renal tubular secretion
Q5. A drug that displaces warfarin from albumin could lead to:
- Decreased free warfarin concentration and reduced effect
- Increased total warfarin concentration with no change in effect
- Increased free warfarin concentration and increased bleeding risk
- Enhanced urinary excretion of warfarin
Correct Answer: Increased free warfarin concentration and increased bleeding risk
Q6. Cimetidine often increases plasma concentrations of co-administered drugs by:
- Inducing CYP3A4-mediated metabolism
- Inhibiting multiple hepatic CYP enzymes
- Chelating drugs in the gut
- Increasing renal tubular secretion
Correct Answer: Inhibiting multiple hepatic CYP enzymes
Q7. Which pharmacokinetic interaction occurs when two drugs compete for the same metabolic enzyme and one increases the other’s concentration?
- Enzyme induction interaction
- Protein binding displacement
- Competitive enzyme inhibition
- Altered enterohepatic recirculation
Correct Answer: Competitive enzyme inhibition
Q8. St. John’s wort can reduce plasma levels of many drugs by which mechanism?
- Inhibition of P-glycoprotein transporters
- Induction of CYP3A4 and P-glycoprotein
- Competing for renal uptake transporters
- Increasing plasma protein binding
Correct Answer: Induction of CYP3A4 and P-glycoprotein
Q9. Which interaction is most likely if a drug increases renal tubular pH, altering elimination of a weak acid?
- Decreased ionization leading to increased reabsorption of the weak acid
- Increased ionization leading to greater renal excretion of the weak acid
- No change in renal clearance of the weak acid
- Inhibition of hepatic metabolism of the weak acid
Correct Answer: Increased ionization leading to greater renal excretion of the weak acid
Q10. Which parameter remains unchanged by displacement from plasma proteins, assuming clearance and volume are constant?
- Free (unbound) drug concentration
- Total drug concentration
- Unbound fraction and pharmacologic effect
- Clearance measured for free drug
Correct Answer: Free (unbound) drug concentration
Q11. Which mechanism explains increased bioavailability when first-pass metabolism is inhibited?
- Enhanced renal elimination
- Reduced presystemic hepatic metabolism
- Increased plasma protein binding
- Increased intestinal motility
Correct Answer: Reduced presystemic hepatic metabolism
Q12. A new drug inhibits CYP2D6. Which co-administered drug’s levels are most likely affected?
- Drug primarily metabolized by CYP1A2
- Drug primarily metabolized by CYP2D6
- Drug excreted unchanged in urine
- Drug undergoing conjugation only
Correct Answer: Drug primarily metabolized by CYP2D6
Q13. Enterohepatic recirculation can prolong a drug’s half-life by:
- Reducing absorption from the intestine
- Facilitating repeated reabsorption from bile back to circulation
- Increasing renal secretion into bile
- Enhancing plasma protein binding irreversibly
Correct Answer: Facilitating repeated reabsorption from bile back to circulation
Q14. Which transporter is commonly involved in drug efflux from enterocytes, affecting oral absorption?
- Organic anion transporting polypeptide (OATP)
- P-glycoprotein (P-gp)
- Glucose transporter (GLUT)
- Renal organic cation transporter (OCT)
Correct Answer: P-glycoprotein (P-gp)
Q15. Which statement best describes the effect of a strong CYP3A4 inhibitor on a drug that is a CYP3A4 substrate with a high extraction ratio?
- Little change because hepatic clearance is flow-limited
- Marked increase in oral bioavailability due to reduced first-pass metabolism
- Decrease in AUC due to enhanced renal clearance
- No effect on plasma levels because only protein binding matters
Correct Answer: Marked increase in oral bioavailability due to reduced first-pass metabolism
Q16. Which interaction is an example of pharmacokinetic antagonism at the absorption phase?
- Calcium binding tetracyclines in the gut
- Enzyme induction reducing drug metabolism
- Plasma protein displacement increasing free drug
- Competition for renal tubular secretion
Correct Answer: Calcium binding tetracyclines in the gut
Q17. If a drug’s clearance doubles while dose remains constant, the steady-state concentration will:
- Double
- Remain unchanged
- Halve
- Increase fourfold
Correct Answer: Halve
Q18. Which genetic factor can alter drug interactions by changing enzyme activity?
- Polymorphism in CYP450 genes
- Variability in gastric pH only
- Differences in plasma albumin levels only
- Age-related renal blood flow changes only
Correct Answer: Polymorphism in CYP450 genes
Q19. A patient on digoxin starts verapamil. Which pharmacokinetic interaction is most likely to increase digoxin levels?
- Induction of digoxin metabolism in liver
- Inhibition of P-glycoprotein leading to reduced efflux
- Increased renal excretion via OAT inhibition
- Displacement from plasma proteins
Correct Answer: Inhibition of P-glycoprotein leading to reduced efflux
Q20. Which change suggests a drug interaction due to enzyme induction over time?
- Immediate increase in AUC after a single dose of inducer
- Gradual decrease in AUC of the affected drug over days to weeks
- Rapid increase in free fraction due to displacement
- Instantaneous change in urinary pH
Correct Answer: Gradual decrease in AUC of the affected drug over days to weeks
Q21. Which drug pair illustrates a classic metabolic inhibition interaction increasing toxicity risk?
- Rifampin and oral contraceptives
- Ketoconazole and cisapride
- Probenecid and penicillin
- Warfarin and rifampin
Correct Answer: Ketoconazole and cisapride
Q22. Which mechanism explains why antacids reduce absorption of some drugs?
- Altering gastric pH and forming complexes with drugs
- Inducing intestinal CYP enzymes
- Increasing hepatic blood flow
- Enhancing renal tubular reabsorption
Correct Answer: Altering gastric pH and forming complexes with drugs
Q23. A prodrug requiring CYP2C19 activation will have reduced effect when co-administered with:
- A CYP2C19 inducer
- A CYP2C19 inhibitor
- An enzyme that increases renal excretion
- A drug that increases plasma protein binding
Correct Answer: A CYP2C19 inhibitor
Q24. Which clinical consequence is most likely when a narrow therapeutic index drug undergoes enzyme inhibition?
- Subtherapeutic effect without risk
- Potential toxicity due to elevated plasma concentrations
- Enhanced excretion making dosing easier
- No clinical significance for monitoring
Correct Answer: Potential toxicity due to elevated plasma concentrations
Q25. What is the effect of food that slows gastric emptying on the Tmax of an orally absorbed drug?
- Tmax decreases (occurs earlier)
- Tmax increases (delayed)
- No change in Tmax
- Immediate increase in clearance
Correct Answer: Tmax increases (delayed)
Q26. Which describes a drug interaction where one agent increases the free fraction but total clearance is unchanged, leading to increased elimination of the free drug?
- Irreversible protein binding increasing half-life
- Protein binding displacement with clearance unchanged
- Induction of renal transporters decreasing free drug
- Inhibition of CYP enzymes increasing total drug
Correct Answer: Protein binding displacement with clearance unchanged
Q27. Which laboratory change would indicate decreased hepatic metabolism of a drug due to inhibitor co-administration?
- Decreased AUC and decreased half-life
- Increased AUC and increased half-life
- Unchanged AUC and decreased clearance
- Decreased Cmax with faster elimination
Correct Answer: Increased AUC and increased half-life
Q28. Co-administration of two drugs excreted via the same renal transporter can cause interaction by:
- Mutual inhibition of transporter-mediated secretion
- Enhancing hepatic glucuronidation
- Altering gastric pH only
- Reducing plasma protein binding exclusively
Correct Answer: Mutual inhibition of transporter-mediated secretion
Q29. Which factor most increases the clinical significance of a pharmacokinetic drug interaction?
- Wide therapeutic index of the affected drug
- Short half-life of the affected drug
- Narrow therapeutic index of the affected drug
- High volume of distribution making plasma levels irrelevant
Correct Answer: Narrow therapeutic index of the affected drug
Q30. When initiating a strong CYP inhibitor in a patient on a statin metabolized by CYP3A4, the appropriate pharmacokinetic consideration is to:
- Increase the statin dose immediately
- Monitor for toxicity and consider dose reduction
- Stop the inhibitor because interactions are impossible to manage
- Ignore the interaction if cholesterol goals are met
Correct Answer: Monitor for toxicity and consider dose reduction
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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