In acidic urine, weak bases are excreted more rapidly because the drug is predominantly in which form?

• A. unionized form
• B. ionized form
• C. neither form
• D. both forms

Answer: (B)

When urine is acidic, weak bases become protonated and form the ionized (charged) species. For bases, the Henderson–Hasselbalch relationship shows that if the urine pH is below the drug’s pKa, most of the drug exists as BH+, the ionized form. Ionized molecules are water-soluble and don’t cross back through the renal tubule membranes easily, so they aren’t reabsorbed and are excreted more rapidly in the urine. If the drug were in the unionized form, it would be more readily reabsorbed, slowing excretion. For example, with a base that has a pKa around 7, at pH 5 the ratio BH+/B is about 100:1, so essentially the entire drug is ionized.