A drug with very high tissue affinity will typically exhibit which combination of plasma concentration and volume of distribution?

• A. High plasma concentration and low VD
• B. Low plasma concentration and high VD
• C. High plasma concentration and high VD
• D. Low plasma concentration and low VD

Answer: (B)

When a drug has very high tissue affinity, it moves out of the blood and into tissues extensively. This means only a small fraction stays in the plasma for a given dose, so the plasma concentration becomes low. The volume of distribution is a theoretical measure that relates the total amount of drug in the body to its plasma concentration (Vd = amount in body / plasma concentration). If most of the drug is in tissues, the plasma concentration is small, but the amount in the body is still large, which drives Vd up. So the expected pattern is a low plasma concentration paired with a high volume of distribution. For an IV bolus, C0 = Dose / Vd, so a large Vd leads to a low initial plasma concentration. A higher Vd can also mean a longer half-life, since the drug is stored in tissues and released slowly back into the plasma.