Pharmacology · Pharmacokinetics and Pharmacodynamics

A drug has a volume of distribution (Vd) of 500 L in a 70 kg adult. Which pharmacokinetic conclusion is most accurate about this drug?

  • A The drug is extensively bound to plasma proteins and remains in the vascular compartment
  • B The drug is extensively distributed into tissues, with very low plasma concentrations relative to the total body load
  • C The drug has a Vd close to total body water (42 L), indicating even distribution
  • D The drug cannot be removed by hemodialysis, because high Vd implies extensive renal excretion
Correct answer: B. The drug is extensively distributed into tissues, with very low plasma concentrations relative to the total body load

Explanation

Volume of distribution (Vd) is a mathematical concept representing the apparent volume in which a drug is distributed if it were at the same concentration throughout as in plasma. A Vd of 500 L far exceeds total body volume (70 L) and all physiological compartments (plasma ~3 L, interstitial ~12 L, intracellular ~27 L, total body water ~42 L), indicating the drug accumulates extensively in deep tissue compartments (e.g., adipose, muscle, intracellularly), leaving very little in plasma. Drugs with large Vd (like chloroquine ~200-800 L/kg, amiodarone) are NOT easily removed by hemodialysis because most drug is in tissues, not plasma. High plasma protein binding produces a small Vd (option A).

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

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