A drug is given orally at 200 mg. Absolute bioavailability is 50%. Plasma protein binding is 90%. If the apparent volume of distribution is 20 L, what is the amount of drug distributed in the plasma compartment (assuming plasma volume ~3 L) versus tissues?

• A All 100 mg is in plasma; none enters tissues because protein binding retains it
• B Dose absorbed = 100 mg; plasma concentration = 100/3 = 33.3 mg/L; all drug is in plasma
• C Dose absorbed = 100 mg; plasma concentration = 200/20 = 10 mg/L because bioavailability is not used in PK calculations
• D Dose absorbed = 100 mg; total body load = 100 mg across Vd 20 L. Plasma concentration = 100/20 = 5 mg/L; drug in plasma = 5 mg/L × 3 L = 15 mg; remainder (85 mg) is in tissues ✓

Explanation

Bioavailable dose = 200 mg × 0.50 = 100 mg. At apparent equilibrium: Cp = Dose/Vd = 100 mg / 20 L = 5 mg/L. Drug in plasma = Cp × plasma volume = 5 mg/L × 3 L = 15 mg. Drug in tissues = 100 − 15 = 85 mg. High protein binding keeps drug in plasma but Vd reflects the apparent distribution including the protein-bound fraction; the drug effectively distributes as if in 20 L due to tissue binding offsetting plasma protein binding in this example. True volume of distribution incorporates both plasma protein and tissue binding.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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