Cytochrome P450 based drug interactions MCQs With Answer

This quiz collection on Cytochrome P450 (CYP)-based drug interactions is tailored for M.Pharm students studying Modern Bio‑Analytical Techniques (MPA 202T). It focuses on the biochemical mechanisms, clinical implications and laboratory approaches used to identify and quantify CYP-mediated interactions. Questions cover major CYP isoforms, common inhibitors and inducers, probe substrates, polymorphism effects, in vitro assay design (microsomes, hepatocytes, recombinant enzymes), kinetic parameters (IC50, Ki, kinact), time‑dependent inhibition, and in vitro–in vivo extrapolation. Use these MCQs to test and deepen your understanding of how CYP interactions affect drug exposure, safety and therapeutic outcomes, and how bioanalytical methods detect and predict such interactions.

Q1. Which CYP isoform is primarily responsible for the metabolism of approximately 50% of marketed drugs and is a common source of clinically significant drug interactions?

• CYP1A2
• CYP2D6
• CYP2C9
• CYP3A4

Correct Answer: CYP3A4

Q2. Grapefruit juice increases systemic exposure of certain orally administered drugs mainly by which mechanism?

• Induction of hepatic CYP2C9 expression
• Mechanism‑based irreversible inhibition of intestinal CYP3A4
• Competitive inhibition of renal transporters
• Activation of CYP2D6 enzyme activity

Correct Answer: Mechanism‑based irreversible inhibition of intestinal CYP3A4

Q3. A patient taking simvastatin is prescribed clarithromycin. The most likely pharmacokinetic consequence is:

• Decreased simvastatin absorption due to pH changes
• Increased simvastatin plasma concentration due to CYP3A4 inhibition
• Enhanced simvastatin renal clearance via P‑glycoprotein induction
• No change because clarithromycin is a CYP2D6 inducer

Correct Answer: Increased simvastatin plasma concentration due to CYP3A4 inhibition

Q4. Which experimental system is most appropriate for initial screening of CYP-mediated metabolic stability and reaction phenotyping in vitro?

• Human plasma protein binding assay
• Human liver microsomes (HLM)
• Whole blood culture
• Renal cortical membrane preparations

Correct Answer: Human liver microsomes (HLM)

Q5. Time‑dependent inhibition (TDI) of a CYP enzyme is best characterized by which pair of kinetic parameters?

• Km and Vmax
• IC50 and EC50
• kinact and KI
• Cmax and Tmax

Correct Answer: kinact and KI

Q6. Which statement correctly describes a mechanism‑based inactivator (suicide inhibitor) of CYP enzymes?

• It reversibly binds to the active site without chemical modification
• It is metabolized by the CYP to a reactive intermediate that covalently modifies the enzyme
• It increases enzyme synthesis by activating nuclear receptors
• It only affects transporters, not CYPs

Correct Answer: It is metabolized by the CYP to a reactive intermediate that covalently modifies the enzyme

Q7. Which probe substrate is commonly used to phenotype CYP2D6 activity in vivo?

• Midazolam
• Dextromethorphan
• Warfarin (S‑enantiomer)
• Caffeine

Correct Answer: Dextromethorphan

Q8. A strong CYP2C19 inhibitor would most likely cause which change in the pharmacokinetics of omeprazole (a CYP2C19 substrate)?

• Decreased AUC and increased clearance
• No effect on bioavailability
• Increased AUC and prolonged half‑life
• Increased renal elimination of omeprazole

Correct Answer: Increased AUC and prolonged half‑life

Q9. Which of the following drug interaction types requires consideration of both CYP metabolism and transporter (e.g., P‑gp) effects for accurate prediction?

• Interactions involving exclusively renal excretion
• Oral drugs with significant first‑pass intestinal CYP3A4 metabolism and P‑gp efflux
• Topical drugs that do not undergo systemic absorption
• Inhaled anesthetics cleared by the lungs

Correct Answer: Oral drugs with significant first‑pass intestinal CYP3A4 metabolism and P‑gp efflux

Q10. In vitro IC50 values are often used to screen for CYP inhibition. Which additional measurement improves prediction of in vivo interaction risk?

• Plasma protein binding and unbound inhibitor concentration (fu and Iu)
• Blood glucose concentration
• Red blood cell count
• Renal clearance of the inhibitor

Correct Answer: Plasma protein binding and unbound inhibitor concentration (fu and Iu)

Q11. Which genetic phenotype of CYP2D6 is most likely to cause therapeutic failure with codeine due to reduced conversion to morphine?

• Ultrarapid metabolizer
• Extensive metabolizer
• Poor metabolizer
• Intermediate inducer

Correct Answer: Poor metabolizer

Q12. Rifampicin causes clinically significant drug interactions largely by which mechanism?

• Competitive inhibition of CYP3A4 active site
• Induction of CYP enzymes via activation of the pregnane X receptor (PXR)
• Direct covalent modification of CYP proteins
• Blocking renal transporters non‑specifically

Correct Answer: Induction of CYP enzymes via activation of the pregnane X receptor (PXR)

Q13. Which analytical approach is commonly used in bioanalysis to quantify parent drug and metabolites to assess CYP‑mediated interactions?

• HPLC–UV with no mass detection
• LC–MS/MS with validated multiple reaction monitoring (MRM) assays
• Gel electrophoresis
• Fluorescence microscopy

Correct Answer: LC–MS/MS with validated multiple reaction monitoring (MRM) assays

Q14. What is the principal consequence when a patient who is an ultrarapid CYP2D6 metabolizer receives standard doses of tramadol?

• Reduced analgesia due to decreased formation of active metabolite
• Increased risk of opioid toxicity from higher active metabolite formation
• No clinical effect because tramadol is not metabolized by CYP2D6
• Enhanced renal clearance of tramadol

Correct Answer: Increased risk of opioid toxicity from higher active metabolite formation

Q15. In vitro–in vivo extrapolation (IVIVE) of CYP induction data commonly requires which of the following to predict clinical induction magnitude?

• Only in vitro IC50 values
• Induction Emax and EC50 combined with hepatic scaling factors and unbound plasma concentration
• Protein melting temperature data
• Renal filtration fraction

Correct Answer: Induction Emax and EC50 combined with hepatic scaling factors and unbound plasma concentration

Q16. Which inhibitor would be classified as a “strong” CYP3A4 inhibitor according to FDA guidance and likely require dose adjustment of sensitive substrates?

• Ketoconazole
• Caffeine
• Amoxicillin
• Omeprazole

Correct Answer: Ketoconazole

Q17. When evaluating time‑dependent CYP inhibition in vitro, which experimental design element distinguishes TDI from reversible inhibition?

• Measuring inhibition at a single time point only
• Pre‑incubation of inhibitor with enzyme and NADPH before adding substrate
• Excluding NADPH from all incubations
• Using only buffer without microsomal protein

Correct Answer: Pre‑incubation of inhibitor with enzyme and NADPH before adding substrate

Q18. A new drug shows selective metabolism by CYP1A2 in vitro. Which co‑medication or exposure is likely to increase its clearance in vivo?

• Ciprofloxacin (a CYP1A2 inhibitor)
• Smoking (polycyclic aromatic hydrocarbon induction of CYP1A2)
• Fluconazole (CYP2C9 inhibitor)
• Grapefruit juice (intestinal CYP3A4 inhibitor)

Correct Answer: Smoking (polycyclic aromatic hydrocarbon induction of CYP1A2)

Q19. Which situation best exemplifies a pharmacokinetic drug–drug interaction due to competitive inhibition?

• A drug increases transcription of CYP genes via nuclear receptor binding
• Two drugs that are substrates for the same CYP isoform administered simultaneously, where one reversibly occupies the active site
• A drug alkylates CYP creating irreversible enzyme loss
• A drug altering gastric pH affecting dissolution only

Correct Answer: Two drugs that are substrates for the same CYP isoform administered simultaneously, where one reversibly occupies the active site

Q20. In bioanalytical method development for DDI studies, why is it important to quantify both parent drug and major metabolites?

• Metabolites are always inactive and unimportant
• Parent quantification alone cannot reveal shifts in metabolic pathways, formation of active/toxic metabolites, or changes in metabolic clearance
• Regulatory agencies prohibit metabolite analysis
• Measuring metabolites is only useful for topical formulations

Correct Answer: Parent quantification alone cannot reveal shifts in metabolic pathways, formation of active/toxic metabolites, or changes in metabolic clearance

Download