Pharmacokinetics and Drug Calculations Flashcards

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?

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.

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?

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.

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.

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.

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)?

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.

What is the significance of calculating the creatinine clearance (CrCl) before prescribing an antibiotic such as nitrofurantoin?

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.

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?

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.