A drug has a volume of distribution (Vd) of 700 L. What does this pharmacokinetic parameter indicate about the drug's distribution?

• A The drug distributes only in plasma water (3–5 L), suggesting extensive plasma protein binding
• B The drug is confined to the extracellular fluid (14 L), typical of a large hydrophilic molecule
• C The drug has a Vd equal to total body water (42 L), indicating equal distribution between plasma and intracellular fluid
• D The drug is extensively sequestered in deep tissue compartments (lipid stores, muscle, intracellular organelles), with very low plasma concentrations relative to total body drug content ✓

Explanation

Volume of distribution (Vd) is a pharmacokinetic concept that does NOT represent a real physiological volume but rather a hypothetical volume that would be needed to contain the total body dose at the measured plasma concentration. A very large Vd (e.g. 500–1000 L) — far exceeding total body water (~42 L) — indicates that the drug is extensively sequestered in peripheral tissue compartments (adipose tissue, muscle, liver, intracellular organelles), resulting in very low plasma concentrations relative to total body drug content. Classic examples: chloroquine (Vd ~200–800 L/kg), amiodarone (Vd ~60 L/kg), and chlorpromazine (Vd ~20 L/kg). This has clinical implications: these drugs cannot be removed by haemodialysis.

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

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Written and medically reviewed by the StethoPrep medical team.