If a fixed IV dose is given, what happens to C0 as Vd increases?

• A. C0 increases
• B. C0 remains the same
• C. C0 decreases
• D. C0 becomes negative

Answer: (C)

When a fixed IV dose is given, the initial plasma concentration is determined by C0 = D / Vd. This means the same dose is spread into a larger apparent volume as Vd increases, so the concentration in the plasma at time zero drops. For example, with a 100 mg dose, if Vd is 10 L, C0 is 10 mg/L; if Vd increases to 50 L, C0 drops to 2 mg/L. It can’t become negative, and it can’t stay the same or rise with a larger Vd. Therefore, C0 decreases as Vd increases.