For a drug eliminated by first-order kinetics from a one-compartment model, which change will prolong its elimination half-life?

• A Increasing clearance while volume of distribution stays constant
• B Decreasing volume of distribution while clearance stays constant
• C Reducing the administered dose
• D Increasing volume of distribution while clearance stays constant ✓

Explanation

Half-life is governed by the equation t1/2 = 0.693 x Vd / CL. It is therefore directly proportional to volume of distribution and inversely proportional to clearance. A larger Vd with unchanged clearance means less drug is presented to the eliminating organs per unit time, so half-life lengthens. Reducing the dose lowers the starting concentration but leaves both Vd and CL untouched, so half-life is unchanged, which is the defining feature of first-order elimination.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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