A 22-year-old woman is brought to the emergency department 6 hours after ingesting a large quantity of aspirin. Arterial pH is 7.28 and urinary pH is 5.5. The internist orders intravenous sodium bicarbonate. The pharmacokinetic rationale for this intervention is:

• A Alkalinization increases tubular reabsorption of salicylate, prolonging its half-life
• B Alkalinization inhibits the cytochrome P450 metabolism of salicylate
• C Alkalinization displaces salicylate from plasma albumin, increasing free drug levels
• D Alkalinization ionizes salicylate in the tubular lumen, trapping it and increasing renal clearance ✓

Explanation

Salicylic acid is a weak acid with a pKa around 3.5. Raising urinary pH shifts the Henderson-Hasselbalch equilibrium toward the ionized, lipid-insoluble form in the tubular lumen, so the drug cannot diffuse back across the tubular epithelium. This ion trapping greatly enhances renal excretion and is standard management in moderate salicylate poisoning. Option A states the opposite of the true effect, and options C and B describe mechanisms unrelated to urinary pH manipulation.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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