If a drug is highly bound to tissue proteins, how does this affect half-life?

• A. Shorter half-life
• B. Longer half-life
• C. No change
• D. Variable

Answer: (A)

When a drug binds a lot to tissue proteins, it increases the apparent volume of distribution because much of the drug is stored in tissues rather than circulating freely in plasma. Clearance mainly removes the unbound drug, so as more drug is sequestered in tissues, less is available for rapid elimination. The half-life is determined by t1/2 ≈ 0.693 × (Vd / CL). If Vd goes up while clearance stays the same or doesn’t rise as fast, the half-life increases. So strong tissue binding tends to prolong the drug’s half-life, even though the initial plasma concentration may drop quickly due to distribution into tissues.