A 19-year-old woman presents 5 hours after ingesting a large quantity of salicylate tablets. Along with supportive care, urinary alkalinization is planned. The pharmacokinetic basis for alkalinizing the urine in this poisoning is:

• A Ionized salicylate formed in alkaline urine cannot back-diffuse across tubular epithelium ✓
• B Alkalinization increases active tubular secretion of salicylate
• C Alkalinization displaces salicylate from plasma albumin into the tubular lumen
• D Alkaline urine increases glomerular filtration of salicylate

Explanation

Salicylic acid is a weak acid. Raising urine pH above its pKa shifts the Henderson-Hasselbalch equilibrium toward the ionized form, which is lipid insoluble and trapped within the tubular lumen, preventing passive back-diffusion and enhancing net excretion. Glomerular filtration depends on free plasma concentration and is unaffected by luminal pH, and salicylate leaves the lumen by passive diffusion rather than being actively secreted back.

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

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