How would a higher affinity drug affect half-life?

• A. Higher affinity would shorten the half-life
• B. Higher affinity would lengthen the half-life
• C. There would be no effect on half-life
• D. It would increase clearance

Answer: (B)

Higher affinity means the drug binds more tightly to its target, which can slow its elimination and keep it in the body longer. Half-life reflects how long the drug stays in systemic circulation, and is influenced by how quickly it is cleared relative to how much is distributed. When binding to the target sequesters the drug or creates a larger bound reservoir, the effective clearance drops or the apparent volume of distribution increases, both of which raise the half-life. In many practical contexts, stronger target binding leads to longer persistence in the body. (Note: in some nonlinear systems, very high affinity can complicate clearance, but the common teaching is that higher affinity tends to lengthen the half-life.)