If a lipophilic drug is dosed in a patient with increased adiposity leading to a larger apparent volume of distribution, how might this affect half-life and dosing?

• A. Decrease
• B. Increased Vd in adipose tissue prolongs t1/2
• C. No change
• D. Shorter t1/2

Answer: (B)

The key idea is that a drug’s half-life depends on both how it distributes in the body (Vd) and how fast it is cleared (CL): t1/2 ≈ 0.693 × Vd / CL. For a lipophilic drug, more adipose tissue means the drug can distribute more widely into fat, increasing the apparent volume of distribution. If clearance stays the same, this larger Vd makes the half-life longer.

With a longer half-life, the drug takes more time to accumulate to steady-state with repeated dosing and to be cleared after stopping. That means dosing intervals may need to be extended to avoid buildup, and for rapid attainment of a target concentration, a larger loading dose (proportional to the increased Vd) may be required. In short, increased Vd in adipose tissue prolongs t1/2, which is why the correct statement says the half-life is prolonged.