How does obesity typically affect the volume of distribution for lipophilic drugs?

• A. Obesity can increase Vd for lipophilic drugs.
• B. Obesity decreases Vd for lipophilic drugs.
• C. Obesity has no effect on Vd.
• D. Obesity only affects clearance.

Answer: (A)

Obesity increases the volume of distribution for lipophilic drugs. Lipophilic compounds preferentially partition into adipose tissue, and with more fat mass there is a larger reservoir for these drugs. This means a greater amount of drug can spread out of the plasma into tissues for a given plasma concentration, raising the Vd (Vd = total amount in the body divided by plasma concentration). A higher Vd can also lengthen the drug’s apparent half-life if clearance remains unchanged, since t1/2 is proportional to Vd. The key idea is that fat tissue serves as a storage site for lipophilic drugs, and more fat shifts distribution toward a larger Vd.