If a drug is mostly unbound in plasma, distribution is most affected by which parameter?

• A. Absorption
• B. Distribution
• C. Metabolism
• D. Excretion

Answer: (B)

When a drug is mostly unbound in plasma, its ability to move from the blood into tissues drives distribution. Only the unbound fraction can diffuse across capillary walls and partition into tissues, so how widely and quickly the drug distributes is determined by distribution factors such as tissue perfusion and membrane permeability, as well as the drug’s lipophilicity and tissue affinity. Absorption concerns entry into the systemic circulation, while metabolism and excretion are elimination processes that remove drug from the body. Because the question focuses on how the drug spreads after it's in plasma, the distribution process itself is the key factor.