TDM examples: Methotrexate, 5-FU, Cisplatin, Meropenem MCQs With Answer

TDM examples: Methotrexate, 5-FU, Cisplatin, Meropenem — MCQs With Answer

This quiz set is designed for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. It covers practical and conceptual aspects of TDM for four important drugs: methotrexate, 5-fluorouracil (5-FU), cisplatin and meropenem. Questions emphasize sampling times, therapeutic targets, dose adjustment principles, toxicity markers, assay considerations and special clinical situations such as renal impairment, DPD deficiency, haemodialysis and continuous infusions. The goal is to strengthen understanding of when and how TDM informs safe and effective chemotherapy and antimicrobial dosing, and to prepare students for real-world monitoring challenges and decisions in clinical pharmacy practice.

Q1. Which of the following is the standard recommended plasma sampling schedule for therapeutic drug monitoring after high‑dose methotrexate therapy to assess clearance?

  • Samples at 1, 6 and 12 hours post infusion
  • Samples at 24, 48 and 72 hours post infusion
  • Samples daily for 7 days
  • A single trough sample at 24 hours is sufficient

Correct Answer: Samples at 24, 48 and 72 hours post infusion

Q2. Which plasma methotrexate concentration threshold at 48 hours is commonly used to identify delayed elimination and risk of toxicity?

  • > 0.01 μmol/L
  • > 0.1 μmol/L
  • > 1 μmol/L
  • > 10 μmol/L

Correct Answer: > 1 μmol/L

Q3. The antidote administered to mitigate methotrexate toxicity by supplying reduced folate is:

  • Glucarpidase
  • Leucovorin (folinic acid)
  • Pyridoxine (vitamin B6)
  • Calcium folinate

Correct Answer: Leucovorin (folinic acid)

Q4. In a patient with renal failure and very high methotrexate levels, which agent enzymatically degrades extracellular methotrexate and can rapidly lower plasma concentrations?

  • Meropenem
  • Glucarpidase
  • Leucovorin
  • Activated charcoal

Correct Answer: Glucarpidase

Q5. Which analytic method is most commonly used for precise quantification of methotrexate in plasma for TDM?

  • Colorimetric assay
  • High-performance liquid chromatography (HPLC) or LC-MS/MS
  • Rapid antigen test
  • Enzyme immunoassay without validation

Correct Answer: High-performance liquid chromatography (HPLC) or LC-MS/MS

Q6. Which genetic deficiency significantly increases risk of severe 5-FU toxicity and is relevant to pre-treatment testing or consideration in TDM interpretation?

  • UGT1A1 deficiency
  • Thiopurine methyltransferase (TPMT) deficiency
  • Dihydropyrimidine dehydrogenase (DPD) deficiency
  • CYP2D6 ultra-rapid metabolism

Correct Answer: Dihydropyrimidine dehydrogenase (DPD) deficiency

Q7. For continuous infusion 5-FU, therapeutic drug monitoring commonly aims to control which PK metric to guide dose adjustments?

  • Peak plasma concentration (Cmax) only
  • Area under the concentration-time curve (AUC) or steady-state concentration (Css)
  • Time to peak concentration (Tmax)
  • Renal clearance measured by urine collection

Correct Answer: Area under the concentration-time curve (AUC) or steady-state concentration (Css)

Q8. Which clinical strategy reduces 5-FU toxicity in a patient identified with partial DPD deficiency?

  • Increase infusion rate
  • Switch to bolus high-dose 5-FU
  • Reduce dose and/or select alternative non‑DPD‑dependent regimen
  • Add leucovorin rescue

Correct Answer: Reduce dose and/or select alternative non‑DPD‑dependent regimen

Q9. Which statement best describes the primary PK/PD index predictive of meropenem efficacy?

  • The peak/MIC ratio (Cmax/MIC)
  • The time the free drug concentration remains above the MIC (%fT>MIC)
  • The AUC over 24 hours only (AUC24)
  • Protein binding percentage alone

Correct Answer: The time the free drug concentration remains above the MIC (%fT>MIC)

Q10. In critically ill patients with augmented renal clearance, meropenem dosing may require which of the following to maintain pharmacodynamic targets?

  • Standard intermittent bolus dosing only
  • Reduced dose to avoid toxicity
  • Increased dose or prolonged/continuous infusion
  • Switch to aminoglycoside monotherapy

Correct Answer: Increased dose or prolonged/continuous infusion

Q11. When performing TDM for meropenem in patients on continuous renal replacement therapy (CRRT), which factor is most important to consider?

  • Meropenem is not removed by CRRT
  • Filter clearance and CRRT effluent rate affecting extracorporeal clearance
  • Only protein binding changes matter in CRRT
  • Single prefilter concentration is sufficient for all dosing decisions

Correct Answer: Filter clearance and CRRT effluent rate affecting extracorporeal clearance

Q12. Cisplatin major dose‑limiting toxicity that is often monitored clinically rather than by plasma drug level is:

  • Myelosuppression measured by white cell count
  • Nephrotoxicity assessed by serum creatinine and urine output
  • Liver enzyme elevation
  • QT interval prolongation on ECG

Correct Answer: Nephrotoxicity assessed by serum creatinine and urine output

Q13. Which prophylactic measure is most important to reduce cisplatin nephrotoxicity during administration?

  • Co‑administration of NSAIDs
  • Pre- and post‑hydration with saline and forced diuresis
  • Giving cisplatin as a rapid bolus without fluids
  • Omitting antiemetic therapy

Correct Answer: Pre- and post‑hydration with saline and forced diuresis

Q14. Compared to carboplatin, cisplatin dosing is typically based on:

  • Target AUC using the Calvert formula
  • Body surface area (BSA) based dosing
  • Creatinine clearance only
  • Fixed flat dosing for all patients

Correct Answer: Body surface area (BSA) based dosing

Q15. Which laboratory or clinical monitoring is particularly important for early detection of cisplatin ototoxicity?

  • Serum potassium measurement
  • Serial audiometry and patient-reported hearing changes
  • Urine sodium concentration
  • Electrolyte panel every 2 weeks only

Correct Answer: Serial audiometry and patient-reported hearing changes

Q16. Which drug interaction can increase methotrexate toxicity by reducing its renal clearance?

  • Probenecid or high‑dose penicillins
  • Insulin
  • Metformin
  • Levodopa

Correct Answer: Probenecid or high‑dose penicillins

Q17. For 5-FU given as bolus dosing compared with continuous infusion, which pharmacodynamic/toxicity profile is more likely?

  • Less myelosuppression with bolus than infusion
  • Bolus dosing is associated with more myelosuppression and infusion with more hand-foot syndrome and mucositis
  • Identical toxicity profiles regardless of schedule
  • Bolus dosing causes more cardiotoxicity but less gastrointestinal toxicity

Correct Answer: Bolus dosing is associated with more myelosuppression and infusion with more hand-foot syndrome and mucositis

Q18. When collecting blood for therapeutic monitoring of total versus unbound drug concentration (e.g., for highly protein‑bound chemotherapy), important preanalytical consideration is:

  • Use of wrong anticoagulant has no effect
  • Timely separation of plasma and storage at appropriate temperature to prevent artifactual dissociation
  • Delay in processing increases accuracy for unbound levels
  • Light exposure increases protein binding

Correct Answer: Timely separation of plasma and storage at appropriate temperature to prevent artifactual dissociation

Q19. Which statement best describes the clinical role of routine plasma cisplatin concentration TDM in most centers?

  • Routine plasma cisplatin TDM is widely used and essential for dosing
  • Routine TDM is uncommon; clinical monitoring (renal function, electrolytes, audiometry) and supportive care guide therapy
  • Cisplatin levels are routinely used to calculate Calvert AUC
  • TDM is unnecessary because cisplatin has no toxicities

Correct Answer: Routine TDM is uncommon; clinical monitoring (renal function, electrolytes, audiometry) and supportive care guide therapy

Q20. Which rationale best supports performing TDM for meropenem in intensive care unit (ICU) patients?

  • Meropenem has very predictable PK so TDM is never needed
  • ICU patients often have altered volume of distribution and variable clearance (including augmented renal clearance or CRRT), causing risk of under‑ or over‑exposure, so TDM can optimize %fT>MIC
  • TDM is only useful to predict ototoxicity with meropenem
  • The only reason for meropenem TDM is to detect contamination

Correct Answer: ICU patients often have altered volume of distribution and variable clearance (including augmented renal clearance or CRRT), causing risk of under‑ or over‑exposure, so TDM can optimize %fT>MIC

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