A drug with zero-order kinetics is administered at 100 mg/hr by IV infusion. At steady state the plasma concentration is 50 mg/L. If the infusion rate is doubled to 200 mg/hr, what will be the new steady-state plasma concentration?

• A 100 mg/L
• B 200 mg/L
• C The plasma concentration will rise indefinitely without reaching a new steady state
• D It cannot be predicted because zero-order kinetics saturates elimination ✓

Explanation

Zero-order (saturation) kinetics means the drug's elimination capacity is already maximized — a fixed amount is eliminated per unit time regardless of concentration. Because elimination is saturated, increasing the infusion rate beyond that fixed elimination capacity means drug accumulates without reaching a new steady state; plasma levels rise indefinitely and dose-proportional steady-state prediction is not possible. This is the clinical danger of drugs like phenytoin, ethanol, and aspirin (at high doses) that exhibit zero-order kinetics.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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