Which factor is most likely to increase the apparent volume of distribution for a drug?

• A. Increased plasma protein binding
• B. Increased tissue perfusion
• C. High lipophilicity leading to extensive tissue distribution
• D. Decreased tissue affinity

Answer: (C)

The apparent volume of distribution reflects how freely a drug disperses from the bloodstream into body tissues. When a drug is highly lipophilic, it crosses membranes easily and partitions into fats and other tissues, so a large portion leaves the plasma for the tissues. Because the amount in the body is spread out over a smaller plasma concentration, the calculated Vd becomes very large.

Other factors can counteract or not significantly change Vd: increasing plasma protein binding keeps more drug in the blood and reduces distribution to tissues, lowering Vd; faster tissue perfusion changes how quickly the drug distributes but not how far it ultimately goes into tissues; and decreasing tissue affinity reduces tissue uptake, also lowering Vd.