Understanding methods for detecting drug interactions is essential for B. Pharm students to ensure safe and effective therapy. This concise overview highlights key approaches: in vitro assays (CYP inhibition/induction, transporter and protein‑binding studies), in vivo clinical DDI studies, therapeutic drug monitoring, and advanced pharmacokinetic modeling such as PBPK. It also covers pharmacodynamic interaction testing, pharmacogenomics, literature and database screening, spontaneous adverse‑event reporting, and computational prediction tools. Examples include probe substrate studies, Caco‑2 transport assays, hepatocyte incubations, and checkerboard assays for antimicrobials. Mastering these methods helps predict, detect, and manage clinically relevant DDIs. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which in vitro system is most appropriate to assess time‑dependent (mechanism‑based) inhibition of hepatic CYP enzymes?
- Recombinant single CYP isoenzymes without preincubation
- Human liver microsomes with preincubation and NADPH
- Caco‑2 cell monolayers measuring permeability
- Human plasma protein binding assays
Correct Answer: Human liver microsomes with preincubation and NADPH
Q2. Which probe substrate is commonly used to phenotype CYP3A activity in vivo?
- Warfarin
- Midazolam
- Caffeine
- Omeprazole
Correct Answer: Midazolam
Q3. Which method helps predict clinical drug–drug interactions by integrating drug properties, physiology, and dosing?
- Therapeutic drug monitoring (TDM)
- Physiologically based pharmacokinetic (PBPK) modeling
- Protein binding displacement assays
- Checkerboard synergy testing
Correct Answer: Physiologically based pharmacokinetic (PBPK) modeling
Q4. Which in vitro assay is primarily used to evaluate P‑glycoprotein (P‑gp) mediated efflux?
- Human liver microsome CYP inhibition
- Caco‑2 cell monolayer transport assay
- Human hepatocyte induction assay
- Plasma protein binding by ultrafiltration
Correct Answer: Caco‑2 cell monolayer transport assay
Q5. In clinical DDI studies, what design is most efficient for assessing the effect of a perpetrator on a victim drug in healthy volunteers?
- Randomized parallel group with different subjects per arm
- Open‑label fixed‑sequence crossover
- Double‑blind placebo‑controlled parallel
- Case‑control observational
Correct Answer: Open‑label fixed‑sequence crossover
Q6. Which parameter is primarily used to judge the magnitude of a pharmacokinetic interaction?
- Change in AUC (area under the curve)
- Change in melting point of the drug
- Volume of distribution only
- Urine color change
Correct Answer: Change in AUC (area under the curve)
Q7. Which computational approach is used to screen large compound sets for potential CYP inhibitory liability?
- QSAR and molecular docking
- Isobolographic analysis
- Checkerboard microdilution
- Clinical randomized trials
Correct Answer: QSAR and molecular docking
Q8. What does a basic static model “R value” compare when predicting CYP inhibition risk?
- Free fraction in urine to Ki
- Maximum plasma inhibitor concentration to in vitro Ki
- AUC of victim drug to Cmax of victim drug
- Protein binding percentage to clearance
Correct Answer: Maximum plasma inhibitor concentration to in vitro Ki
Q9. Which experimental system can assess both metabolic clearance and induction potential of a new chemical entity?
- Recombinant CYP expressed in bacteria only
- Primary human hepatocytes
- Isolated kidney microsomes
- Platelet aggregation assay
Correct Answer: Primary human hepatocytes
Q10. Which clinical finding suggests a clinically significant pharmacodynamic interaction rather than a pharmacokinetic one?
- Altered AUC with no change in effect
- Enhanced therapeutic effect without change in plasma concentrations
- In vitro enzyme inhibition with no clinical data
- Change in protein binding only
Correct Answer: Enhanced therapeutic effect without change in plasma concentrations
Q11. Which study type is required by regulatory guidance to quantify the magnitude of interaction when a drug is a strong CYP3A inhibitor?
- In vitro microsomal screening only
- Dedicated clinical DDI study using a CYP3A probe substrate
- TDM in a real‑world cohort only
- Animal toxicology study
Correct Answer: Dedicated clinical DDI study using a CYP3A probe substrate
Q12. Which in vitro metric best describes reversible inhibition potency against an enzyme?
- IC50 or Ki
- Protein binding percentage
- Papp in Caco‑2
- Minimum inhibitory concentration (MIC)
Correct Answer: IC50 or Ki
Q13. For transporter‑mediated DDI risk assessment, which parameter is commonly measured in hepatocyte uptake assays?
- Intrinsic clearance by CYP2D6
- Uptake clearance (CLuptake) mediated by OATP
- Fraction unbound in plasma
- Antimicrobial synergy index
Correct Answer: Uptake clearance (CLuptake) mediated by OATP
Q14. What role does therapeutic drug monitoring (TDM) play in detecting drug interactions clinically?
- It measures genetic polymorphisms directly
- It quantifies plasma drug levels to detect altered exposure from DDIs
- It replaces in vitro enzyme assays
- It measures tissue concentrations in liver biopsies routinely
Correct Answer: It quantifies plasma drug levels to detect altered exposure from DDIs
Q15. Which pharmacogenomic factor most commonly influences drug–drug interaction susceptibility?
- Variants in CYP450 genes (e.g., CYP2D6, CYP2C19)
- Blood group antigen type
- Body weight alone
- Urine pH only
Correct Answer: Variants in CYP450 genes (e.g., CYP2D6, CYP2C19)
Q16. Which method is used to detect potential interactions that alter drug protein binding and thus free fraction?
- Ultrafiltration or equilibrium dialysis for plasma protein binding
- Recombinant enzyme induction assay
- Caco‑2 permeability for absorption
- Checkerboard assay for synergy
Correct Answer: Ultrafiltration or equilibrium dialysis for plasma protein binding
Q17. Which analysis helps determine whether two drugs are synergistic, additive, or antagonistic in pharmacodynamics?
- Isobolographic analysis
- CYP inhibition IC50 curve fitting
- PBPK steady‑state simulation only
- Protein binding percentage comparison
Correct Answer: Isobolographic analysis
Q18. Spontaneous adverse event reporting systems (e.g., VigiBase) are useful for:
- Definitive proof of mechanisms of DDI in vitro
- Signal detection of suspected clinical DDIs post‑marketing
- Measuring hepatic microsomal clearance directly
- Predicting PK parameters using PBPK
Correct Answer: Signal detection of suspected clinical DDIs post‑marketing
Q19. Which experimental approach is preferred to assess time‑dependent induction of CYP enzymes?
- Brief exposure of recombinant CYPs without mRNA measurement
- Human hepatocyte cultures measuring mRNA and activity after repeated dosing
- Caco‑2 transport with short incubation
- Equilibrium dialysis for plasma protein binding
Correct Answer: Human hepatocyte cultures measuring mRNA and activity after repeated dosing
Q20. What is the primary utility of a probe drug cocktail in clinical DDI studies?
- To test multiple CYP pathways simultaneously for inhibition or induction
- To measure protein binding of several drugs
- To assess renal clearance only
- To evaluate food effects on drug solubility
Correct Answer: To test multiple CYP pathways simultaneously for inhibition or induction
Q21. Which in vitro system is most suitable to evaluate first‑pass intestinal metabolism?
- Human intestinal microsomes or enterocyte preparations
- Human plasma protein binding assay
- Isolated kidney tubule assay
- Whole blood clotting time assay
Correct Answer: Human intestinal microsomes or enterocyte preparations
Q22. When interpreting an in vitro CYP inhibition result, why is unbound inhibitor concentration important?
- Only bound drug crosses membranes, so bound concentration predicts effect
- Unbound concentration represents the pharmacologically active fraction available to inhibit enzymes
- Unbound concentration is irrelevant for inhibition kinetics
- Total concentration always underestimates interaction potential
Correct Answer: Unbound concentration represents the pharmacologically active fraction available to inhibit enzymes
Q23. Which regulatory threshold often triggers further clinical DDI investigation when a perpetrator increases victim drug AUC?
- Any change in Cmax regardless of magnitude
- A predefined fold‑change in AUC (commonly ≥2‑fold) depending on safety margin
- Only changes in half‑life are considered
- Changes in plasma color
Correct Answer: A predefined fold‑change in AUC (commonly ≥2‑fold) depending on safety margin
Q24. Checkerboard microdilution is primarily used to detect interactions between which drug classes?
- Antimicrobials (antibiotics/antifungals)
- Antidepressants and antipsychotics
- Cardiac glycosides and diuretics
- Proton pump inhibitors only
Correct Answer: Antimicrobials (antibiotics/antifungals)
Q25. Which database is commonly used by pharmacists for checking clinically significant drug interactions?
- Micromedex or Lexicomp
- GenBank sequence repository
- Protein Data Bank (PDB)
- ClinicalTrials.gov only
Correct Answer: Micromedex or Lexicomp
Q26. Mechanism‑based inactivation (MBI) of CYP enzymes is characterized by:
- Immediate reversible inhibition that disappears after dilution
- Irreversible or quasi‑irreversible loss of enzyme activity requiring new enzyme synthesis
- Only induction of enzyme expression
- Changes in membrane permeability only
Correct Answer: Irreversible or quasi‑irreversible loss of enzyme activity requiring new enzyme synthesis
Q27. Which PK sampling strategy is essential in a clinical DDI study to capture AUC accurately?
- Only a single trough sample
- Intensive serial sampling covering absorption, distribution, and elimination phases
- Only urine sampling
- Only a single peak sample
Correct Answer: Intensive serial sampling covering absorption, distribution, and elimination phases
Q28. In vitro to in vivo extrapolation (IVIVE) often requires which key inputs?
- In vitro clearance, plasma protein binding, and physiological scaling factors
- Only in vitro IC50 values without any scaling
- Molecular weight and color of drug powder
- Clinical trial recruitment rates
Correct Answer: In vitro clearance, plasma protein binding, and physiological scaling factors
Q29. Which clinical factor can alter the magnitude of a DDI by changing the victim drug unbound fraction?
- Hypoalbuminemia decreasing protein binding
- Change in genetic code of CYP enzymes overnight
- Ambient room temperature during dosing
- Drug color formulation
Correct Answer: Hypoalbuminemia decreasing protein binding
Q30. Which approach combines literature review, in vitro data, and basic modeling to decide whether a clinical DDI study is necessary?
- Case report submission only
- Tiered risk assessment and decision tree (stepwise DDI risk assessment)
- Random guessing based on chemical name
- Therapeutic drug monitoring without prior assessment
Correct Answer: Tiered risk assessment and decision tree (stepwise DDI risk assessment)
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.
Mail- Sachin@pharmacyfreak.com