Which relationship best describes the effect of extensive tissue distribution on elimination rate?

• A. High Vd with rapid elimination
• B. High Vd with slow elimination
• C. Low Vd with rapid elimination
• D. Low Vd with slow elimination

Answer: (B)

Extensive tissue distribution raises the apparent volume of distribution (Vd). When Vd is large and clearance (Cl) remains unchanged, the elimination half-life t1/2 = 0.693 × Vd / Cl increases, so the observed rate of elimination from the body slows. In other words, the drug sits in tissues like a reservoir and takes longer to be cleared, making elimination slower despite potentially maintaining the same total clearance. This is why the best description is high Vd with slow elimination. If clearance rose in step with distribution, the effect could differ, but with a high Vd and typical constant clearance, elimination is slower.