Pharmacokinetics and Drug Calculations Flashcards

A drug has linear pharmacokinetics. The steady-state concentration at 100 mg/day is 5 mg/L. What steady-state concentration is expected at 200 mg/day?

Answer: 10 mg/L — linear kinetics means proportional increases

Linear (first-order) pharmacokinetics means Css is directly proportional to dose. Doubling the dose doubles the steady-state concentration: 100 mg → 5 mg/L, so 200 mg → 10 mg/L. This predictability is the basis of dose titration for most drugs. Phenytoin is a major exception (non-linear kinetics).

A pharmacist calculates the minimum inhibitory concentration (MIC) breakpoint. An antibiotic has a plasma Cmax of 10 mg/L and the MIC is 0.5 mg/L. What is the Cmax/MIC ratio?

Answer: 20 — suggests adequate concentration-dependent killing (target >8–10 for aminoglycosides)

Cmax/MIC = 10 mg/L / 0.5 mg/L = 20. For concentration-dependent antibiotics (aminoglycosides, fluoroquinolones), a Cmax/MIC of ≥8–10 predicts optimal bacterial killing and prevents resistance. A ratio of 20 exceeds the target and indicates excellent antibacterial exposure.

A patient takes a 500 mg dose of an antibiotic with an oral bioavailability of 80%, a Vd of 40 L, and a half-life of 8 hours. What is the theoretical peak plasma concentration (Cmax) after the first oral dose?

Answer: 10 mg/L

Amount absorbed = 500 × 0.80 = 400 mg. Cmax (simplified, assuming instant absorption) = Dose absorbed / Vd = 400 mg / 40 L = 10 mg/L. In practice, absorption takes time (Tmax) and Cmax is lower than this calculated value. This represents the theoretical maximum.

A pharmacist is asked to compare the half-life of two formulations: regular-release (t½ = 6 hours) vs. extended-release (ER, t½ = 12 hours). How many days does the ER formulation take to reach steady state?

Answer: 2.5 days (5 half-lives of 12 hours = 60 hours ≈ 2.5 days)

The ER formulation's apparent half-life is 12 hours (due to slower release rate). Steady state requires 4–5 half-lives: 5 × 12 hours = 60 hours = 2.5 days. The immediate-release formulation reaches steady state in 5 × 6 = 30 hours = 1.25 days. Extended-release formulations take longer to reach steady state because the absorption phase prolongs the apparent half-life.

The renal clearance of a drug is 60 mL/min and the filtration fraction is 0.20. The free plasma concentration is 5 mg/L. What is the filtered load per minute?

Answer: 0.6 mg/min (GFR × free concentration = 120 mL/min × 0.20 = 24 mL/min is the filtered fraction...

GFR ≈ 120 mL/min in a normal adult. Filtered load = GFR × free drug concentration = 120 mL/min × 5 mg/L = 120 mL/min × 0.005 mg/mL = 0.6 mg/min. Renal clearance (60 mL/min) vs. filtered load (0.6 mg/min) indicates net reabsorption is occurring (since CLrenal < GFR).

A pharmacist is asked about the difference between 'drug clearance' and 'volume of distribution' in terms of their effect on half-life. Which statement is correct?

Answer: Half-life increases when Vd increases (more drug in tissues, slower return to plasma for clearance) or when CL decreases (slower elimination)

t½ = (0.693 × Vd) / CL. Half-life is DIRECTLY proportional to Vd (larger Vd = longer half-life, drug sequestered in tissues) and INVERSELY proportional to CL (lower clearance = longer half-life). Both parameters independently affect half-life. Drugs with large Vd or low CL (e.g., amiodarone: Vd >5,000 L, CL very low) have extremely long half-lives.