Saudi Prometric Pharmacist Pharmacokinetics and Drug Calculations 3 — Questions and Answers
Question 1: A patient requires vancomycin with an AUC/MIC target of 400–600 mg·h/L. The MIC of the organism is 1 mg/L. The measured AUC over 24 hours is 280 mg·h/L. What adjustment is needed?
- Increase the daily dose — current AUC/MIC of 280 is below the target 400–600 (Correct answer)
- Decrease the dose — AUC is too high
- No change — AUC/MIC of 280 is within the therapeutic window
- Switch antibiotic — AUC monitoring is not reliable
Correct answer: Increase the daily dose — current AUC/MIC of 280 is below the target 400–600
Current AUC/MIC = 280/1 = 280, which is below the target of 400–600 mg·h/L for optimal bactericidal activity against MRSA. The daily vancomycin dose should be increased (larger individual doses or more frequent dosing) to achieve the AUC/MIC target. This reflects the shift from trough-based to AUC-guided vancomycin monitoring.
Question 2: A pharmacist is interpreting a drug plasma level drawn 'at trough' for a twice-daily drug with a 12-hour dosing interval. The result is 8 mg/L. The therapeutic range is 5–15 mg/L. What does this indicate?
- Trough is within therapeutic range — continue current dose (Correct answer)
- Trough is below therapeutic range — increase dose
- Trough is above therapeutic range — reduce dose
- Trough levels are not meaningful for twice-daily drugs
Correct answer: Trough is within therapeutic range — continue current dose
A trough level of 8 mg/L falls within the therapeutic range of 5–15 mg/L. This indicates appropriate drug exposure at the lowest point in the dosing interval. If trough is within range and the patient is responding without toxicity, the current regimen should be continued.
Question 3: A drug follows Michaelis-Menten (zero-order, saturable) kinetics. At a plasma concentration below the Km, the drug behaves mostly like:
- First-order kinetics — a constant fraction is eliminated per unit time (Correct answer)
- Zero-order kinetics — a constant amount is eliminated per unit time
- Non-linear kinetics at all concentrations
- Irreversible kinetics that cannot be modeled
Correct answer: First-order kinetics — a constant fraction is eliminated per unit time
Michaelis-Menten kinetics: when [C] << Km, the denominator (Km + C) ≈ Km, and rate = Vmax × C/Km = first-order constant × C. This is first-order behavior. When [C] >> Km, rate ≈ Vmax (constant = zero-order). Phenytoin transitions from first-order to zero-order at therapeutic concentrations because its Km is within the therapeutic range.
Question 4: A patient's phenytoin level is 25 mg/L (toxic range >20 mg/L). The dose was 400 mg/day. Using Michaelis-Menten parameters, if Vmax = 500 mg/day and Km = 4 mg/L, what daily dose maintains a steady-state concentration of 15 mg/L?
- Dose = Vmax × Css / (Km + Css) = 500 × 15 / (4 + 15) = 395 mg/day (Correct answer)
- 250 mg/day
- 450 mg/day
- 375 mg/day
Correct answer: Dose = Vmax × Css / (Km + Css) = 500 × 15 / (4 + 15) = 395 mg/day
At steady state for Michaelis-Menten kinetics: R₀ = Vmax × Css / (Km + Css) = 500 × 15 / (4 + 15) = 7,500 / 19 = 394.7 ≈ 395 mg/day. Reducing from 400 mg to 395 mg/day would bring phenytoin into the therapeutic range. This illustrates phenytoin's sensitivity to small dose changes in the toxic range.
Question 5: A drug is 90% bound to plasma proteins. In a patient with hypoalbuminemia (albumin 2 g/dL instead of normal 4 g/dL), what happens to the free fraction?
- Free fraction approximately doubles from 10% to ~20% — increased pharmacological effect and toxicity risk (Correct answer)
- Free fraction remains unchanged — protein binding adjusts automatically
- Free fraction decreases — hypoalbuminemia reduces drug distribution
- Free fraction becomes 90% — protein binding reverses with low albumin
Correct answer: Free fraction approximately doubles from 10% to ~20% — increased pharmacological effect and toxicity risk
If albumin is halved (2 g/dL vs 4 g/dL) and the drug is 90% protein bound at normal albumin, there are approximately half the binding sites. In simple terms, the free fraction roughly doubles from ~10% to ~20% (actual change depends on concentration and binding constants). For narrow TI drugs (phenytoin, warfarin), this can cause significant toxicity even at 'normal' total drug levels.
Question 6: A patient on continuous renal replacement therapy (CRRT) requires antibiotic dosing. Which pharmacokinetic principle should guide dose adjustment?
- Estimate the drug clearance added by CRRT (based on CRRT effluent rate × drug sieving coefficient) and add to residual renal/hepatic clearance for total clearance (Correct answer)
- Use standard doses — CRRT removes drugs at the same rate as normal kidneys
- Reduce all drug doses by 50% regardless of CRRT clearance
- Stop all renally cleared drugs during CRRT — too difficult to dose
Correct answer: Estimate the drug clearance added by CRRT (based on CRRT effluent rate × drug sieving coefficient) and add to residual renal/hepatic clearance for total clearance
CRRT adds a calculable clearance contribution: CRRT clearance ≈ Effluent rate (L/hr) × Sieving coefficient (Sc). Total clearance = Residual clearance + CRRT clearance. For unbound, water-soluble drugs with Sc near 1 (e.g., many antibiotics), CRRT can significantly supplement drug clearance. Dosing protocols for common antibiotics in CRRT are available in references.
Saudi Prometric Pharmacist Pharmacokinetics and Drug Calculations 3
A patient requires vancomycin with an AUC/MIC target of 400–600 mg·h/L.
The MIC of the organism is 1 mg/L.
The measured AUC over 24 hours is 280 mg·h/L.
What adjustment is needed?