Saudi Prometric Pharmacist Pharmacokinetics and Drug Calculations 4 — Questions and Answers
Question 1: A drug's plasma concentration at time 0 is 50 mg/L. After 10 hours, the concentration is 3.125 mg/L. What is the elimination half-life?
- 2.5 hours (Correct answer)
- 5 hours
- 10 hours
- 1.25 hours
Correct answer: 2.5 hours
From 50 to 3.125 mg/L: 50 → 25 → 12.5 → 6.25 → 3.125 mg/L = 4 half-lives. Time for 4 half-lives = 10 hours. Therefore, half-life = 10/4 = 2.5 hours.
Question 2: A patient is prescribed gentamicin by intermittent infusion. A trough level 30 minutes before the next dose is 3.5 mg/L (desired <2 mg/L). What action is most appropriate?
- Extend the dosing interval — high trough indicates insufficient time for drug to clear between doses (Correct answer)
- Increase the dose — high trough means the drug is distributing too widely
- Reduce the dose but keep the same interval
- Switch to continuous infusion
Correct answer: Extend the dosing interval — high trough indicates insufficient time for drug to clear between doses
An elevated aminoglycoside trough (>2 mg/L for gentamicin with multiple-daily dosing) indicates the drug has not cleared adequately between doses. The solution is to extend the dosing interval — allowing more time for the drug to clear before the next dose. The individual dose amount may also need adjustment based on PK calculations.
Question 3: A patient weighing 80 kg has a serum creatinine of 2.5 mg/dL (age 55, male). Using the Cockcroft-Gault equation, calculate the estimated creatinine clearance.
- CrCl = [(140-55) × 80] / [72 × 2.5] = 37.8 mL/min (Correct answer)
- CrCl = 80/2.5 = 32 mL/min
- CrCl = [(140-55) × 80] / 2.5 = 2,720 mL/min
- CrCl = 80 mL/min (normal for weight)
Correct answer: CrCl = [(140-55) × 80] / [72 × 2.5] = 37.8 mL/min
Cockcroft-Gault: CrCl = [(140 - age) × weight(kg)] / [72 × SCr(mg/dL)] × (0.85 for females). For this patient: [(140-55) × 80] / [72 × 2.5] = [85 × 80] / 180 = 6,800 / 180 = 37.8 mL/min. This indicates moderate renal impairment requiring dose adjustment for renally cleared drugs.
Question 4: After administering a 500 mg oral dose, the AUC is 25 mg·hr/L. After a 100 mg IV dose, the AUC is 12 mg·hr/L. What is the oral bioavailability (F)?
- 41.7% (Correct answer)
- 50%
- 25%
- 120%
Correct answer: 41.7%
F = (AUC_oral / Dose_oral) / (AUC_IV / Dose_IV) = (25/500) / (12/100) = 0.05 / 0.12 = 0.4167 = 41.7%. The calculation normalizes AUC to dose for each route, then takes the ratio. F reflects the fraction of the oral dose reaching systemic circulation compared to the IV standard.
Question 5: What is the significance of calculating the creatinine clearance (CrCl) before prescribing an antibiotic such as nitrofurantoin?
- Nitrofurantoin requires CrCl ≥30–45 mL/min for adequate urinary drug concentration — ineffective AND neurotoxic in severe renal failure (Correct answer)
- CrCl affects nitrofurantoin protein binding only
- CrCl determines nitrofurantoin dose titration between 50–100 mg
- Nitrofurantoin is safe at any CrCl — renal adjustment not required
Correct answer: Nitrofurantoin requires CrCl ≥30–45 mL/min for adequate urinary drug concentration — ineffective AND neurotoxic in severe renal failure
Nitrofurantoin relies on renal excretion for both its mechanism (achieving therapeutic urinary concentrations) and elimination. In severe renal failure (CrCl <30–45 mL/min), drug does not concentrate adequately in urine (therapeutic failure) and inactive metabolites accumulate (peripheral neuropathy, pulmonary toxicity). Nitrofurantoin is contraindicated in significant renal impairment.
Question 6: A pharmacist is conducting TDM for cyclosporine. The trough level is 450 ng/mL (target 100–250 ng/mL). The current dose is 300 mg twice daily. What dose adjustment is appropriate?
- Reduce the dose — calculate target as approximately 55% of current dose (target/current = 200/450 = 0.44 × 300 = 133 mg — approximately 150 mg BD) (Correct answer)
- Increase the dose — the level of 450 is close enough to target
- Switch to IV cyclosporine — oral bioavailability is unreliable
- No change — cyclosporine has a wide therapeutic index
Correct answer: Reduce the dose — calculate target as approximately 55% of current dose (target/current = 200/450 = 0.44 × 300 = 133 mg — approximately 150 mg BD)
Cyclosporine follows relatively linear kinetics within a dosing range. Target midpoint = 175 ng/mL (midpoint of 100–250 range). Required dose ≈ current dose × (target/current level) = 300 × (175/450) ≈ 300 × 0.39 ≈ 117 mg; rounding to 150 mg BD (the nearest practical dose) is appropriate. Close monitoring after any dose change.
Saudi Prometric Pharmacist Pharmacokinetics and Drug Calculations 4
A drug's plasma concentration at time 0 is 50 mg/L.
After 10 hours, the concentration is 3.125 mg/L.
What is the elimination half-life?