A highly lipophilic drug would have which combination of volume of distribution and elimination rate?

• A. Very low Vd; slow elimination
• B. Very high Vd; slow elimination
• C. High Vd; fast elimination
• D. Low Vd; fast elimination

Answer: (B)

A highly lipophilic drug tends to leave the bloodstream and distribute into tissues and fat, so the amount in the body is dispersed over a large volume. This pushes the apparent volume of distribution very high. Since most of the drug isn’t in the plasma, it takes longer for it to cycle back from tissues into the blood to be cleared, making the elimination process slow. The combination of a very large Vd with slow elimination is characteristic of lipophilic drugs, leading to a longer duration of action. The other patterns would imply limited tissue distribution or rapid clearance, which don’t fit the behavior of highly lipophilic compounds.