Volume of Distribution — FRCA Primary MCQ

Correct answer: E — Extensive tissue binding with concentrations in tissues exceeding those in plasma

The correct answer is E. Volume of distribution is an apparent proportionality constant relating the amount of drug in the body to its measured plasma concentration; it is not an anatomical volume. A value of 500 L is far greater than total body water in a 70 kg adult and indicates that relatively little drug remains in plasma because the drug is extensively bound or sequestered in tissues. Digoxin is a clinical example, with a steady-state volume of distribution of approximately 510 L. Distribution into total body water alone would produce a value near 42 L, while extracellular-fluid distribution would be about 14 L. Plasma confinement would produce an even smaller value. Volume of distribution can exceed body mass or any physical fluid compartment, so the estimate is not intrinsically invalid.

Reference: Digoxin 250 microgram/ml solution for injection/infusion, Summary of Product Characteristics, section 5.2 Pharmacokinetic properties—Distribution, revised February 2026. https://www.medicines.org.uk/emc/product/5462/smpc