Which statement about lipophilicity and tissue distribution is correct?

• A. Higher lipophilicity generally leads to smaller Vd
• B. Higher lipophilicity generally leads to larger Vd
• C. Lipophilicity does not influence tissue distribution
• D. Lipophilicity only affects plasma protein binding

Answer: (B)

Lipophilicity drives how a drug partitions between plasma and tissues. As a drug becomes more lipophilic, it readily crosses cell membranes and accumulates in lipid-rich tissues, which lowers its concentration in plasma for a given dose. The volume of distribution is a theoretical space that relates the amount of drug in the body to the concentration in plasma; when the drug is mostly in tissues rather than in the blood, this apparent volume is large. Therefore, higher lipophilicity generally leads to a larger volume of distribution. In contrast, hydrophilic drugs tend to stay in plasma and extracellular fluid, giving a smaller Vd. Lipophilicity does influence tissue distribution and is not limited to plasma protein binding, so the other statements don’t fit.