A drug has a volume of distribution (Vd) of 400 L in a 70 kg patient. What does this signify about the drug's distribution, and what are the implications for dialysis in overdose?

• A The drug is extensively distributed into tissues (lipophilic or tissue-bound); hemodialysis will be ineffective in overdose because only a small fraction resides in the plasma compartment accessible to dialysis ✓
• B The drug is confined to plasma and interstitial fluid; hemodialysis will efficiently remove it in overdose
• C The high Vd means the drug is entirely renally excreted without hepatic metabolism; forced diuresis is the preferred treatment
• D Vd of 400 L indicates the drug undergoes first-pass effect and most is eliminated before systemic distribution

Explanation

Volume of distribution is an apparent, not a real, anatomical volume. Vd = amount of drug in body / plasma concentration. A Vd of 400 L in a 70 kg patient (normal total body water ~42 L, plasma volume ~3.5 L) indicates extensive extravascular tissue binding — the drug is lipophilic or strongly bound to tissue proteins such that only a tiny fraction remains in plasma. Hemodialysis removes drug from plasma; since only ~0.9% of the drug is in plasma at any time (3.5/400 = 0.875%), dialysis removes negligible drug, making it ineffective in overdose. Examples: digoxin (Vd 7 L/kg), TCA antidepressants (Vd 10–50 L/kg). Drugs with low Vd (e.g., lithium, metformin, aminoglycosides) ARE amenable to dialysis.

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

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Written and medically reviewed by the StethoPrep medical team.