A drug has a volume of distribution (Vd) of 500 L in a 70 kg adult. This large Vd most likely indicates:

• A The drug is predominantly distributed in plasma water only
• B The drug is extensively bound to plasma proteins, confining it to the intravascular compartment
• C The drug has very high oral bioavailability and rapid gastrointestinal absorption
• D The drug is extensively distributed into peripheral tissues, with low plasma concentrations relative to total body drug ✓

Explanation

Volume of distribution (Vd) is a mathematical concept representing the apparent volume in which a drug would need to be distributed to account for the observed plasma concentration. A Vd of 500 L far exceeds total body water (~42 L) and even total body volume, indicating that most drug molecules have left the plasma and are sequestered in peripheral tissues (typically lipophilic tissues, adipose, or intracellular compartments). Drugs with large Vd are difficult to remove by hemodialysis (since most drug is not in the plasma) and have long half-lives if tissue-bound. High plasma protein binding would actually give a low-to-moderate Vd (drug stays in plasma). Examples of high-Vd drugs: chloroquine (~200-800 L/kg), amiodarone (~60 L/kg).

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

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