Pharmacology · Pharmacokinetics and Pharmacodynamics

A drug has a volume of distribution (Vd) of 420 L in a 70 kg patient. What does this imply about its distribution and plasma protein binding?

  • A Most of the drug remains in plasma; small Vd indicates high plasma protein binding
  • B The drug is extensively distributed into peripheral tissues or intracellular compartments; Vd >>total body water (42 L) indicates significant tissue sequestration, often associated with high lipophilicity or intracellular ion trapping
  • C The drug is exclusively distributed into the extracellular fluid (Vd = 14 L for ECF)
  • D Very large Vd indicates rapid renal clearance
Correct answer: B. The drug is extensively distributed into peripheral tissues or intracellular compartments; Vd >>total body water (42 L) indicates significant tissue sequestration, often associated with high lipophilicity or intracellular ion trapping

Explanation

Volume of distribution (Vd) is a theoretical volume relating total drug in body to plasma concentration (Vd = Dose/Cp). Total body water is ~42 L (3 L plasma, 11 L interstitial, 28 L intracellular). Vd of 420 L far exceeds total body water, meaning drug has extensively partitioned into tissue compartments, making plasma concentration very low relative to tissue concentrations. This typically reflects high lipophilicity (e.g., amiodarone Vd ~5000 L), high protein binding in tissues, or intracellular ion trapping (e.g., chloroquine in melanin-containing tissues). Large Vd drugs are difficult to dialyze, have long half-lives, and their redistribution (not elimination) determines initial effects.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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