Which statement best describes the effect of clearance on steady-state concentration during continuous IV infusion?

• A. Higher clearance raises Css,avg.
• B. Clearance has no effect on Css,avg.
• C. Css,avg is determined solely by dose rate.
• D. Higher clearance lowers Css,avg.

Answer: (D)

When a drug is given by continuous IV infusion at a constant rate, the steady-state concentration is set by the balance between how fast the drug enters the body and how fast it is cleared. The key relationship is Css,avg = Rate_in / CL. This means that with the same infusion rate, increasing clearance removes drug more quickly, so the steady-state concentration falls. Conversely, lowering clearance would raise Css,avg.

For example, if the infusion rate is 100 mg/hour and clearance is 5 L/hour, Css,avg would be 20 mg/L. If clearance increases to 10 L/hour with the same infusion rate, Css,avg drops to 10 mg/L. This illustrates why higher clearance lowers Css,avg.

The other statements don’t fit because they ignore the essential role of clearance in determining Css at a fixed infusion rate. Css is not determined solely by dose rate; clearance is part of the equation, and increasing clearance reduces the steady-state concentration.