Volume of distribution is a theoretical parameter. What does a Vd greater than total body water suggest?

• A. It implies no distribution beyond plasma
• B. Extensive tissue distribution or binding beyond body water
• C. It indicates low volume of distribution
• D. It indicates high plasma protein binding limited to plasma

Answer: (B)

The question tests how the volume of distribution reflects where a drug goes in the body. Volume of distribution is the theoretical volume that would be needed to contain the total amount of drug in the body at the concentration measured in plasma. It increases as the drug leaves the plasma and distributes into other compartments.

If the Vd is greater than total body water (roughly 0.6 L per kg of body weight, about 42 L for a 70 kg person), it means the drug is not confined to the plasma or to body water. Instead, a large portion is sequestered in tissues or binds to tissue components beyond the aqueous compartments. This can happen with very lipophilic drugs that partition into fat or intracellular spaces, or with drugs that bind strongly to tissue proteins or receptors, creating a reservoir that reduces the amount present in plasma.

So a Vd exceeding total body water points to extensive tissue distribution or tissue binding, which is exactly what option means. In contrast, a small Vd would suggest the drug mainly stays in plasma or extracellular fluid, not outside body water. High plasma protein binding that limits distribution would typically keep the drug within plasma, not push the Vd above body water.