In obesity, for a lipophilic drug, how would the volume of distribution and loading dose change compared with a non-obese individual?

• A. Vd decreases; loading dose decreases.
• B. Vd increases; loading dose increases proportional to Vd.
• C. Vd remains unchanged; loading dose unchanged.
• D. Vd increases; loading dose decreases.

Answer: (B)

Lipophilic drugs spread into fat tissue, so in obesity the expanded fat mass increases the apparent volume of distribution. When you want to rapidly reach a target plasma concentration, the loading dose is calculated as LD = Vd × target concentration. If Vd increases, the loading dose must increase in proportion to reach the same target concentration. So in obesity, for a lipophilic drug, both Vd and the loading dose increase proportionally.