A 68-year-old man with type 2 diabetes on glyburide presents with recurrent episodes of severe hypoglycemia requiring hospitalization. His eGFR is 38 mL/min/1.73 m². Which pharmacokinetic property of glyburide best explains this complication?
- A It is metabolized primarily by CYP2C9 to inactive metabolites
- B It undergoes extensive hepatic first-pass metabolism
- C It has active renal metabolites that accumulate in renal impairment ✓
- D It is a short-acting sulfonylurea with rapid clearance
Correct answer: C. It has active renal metabolites that accumulate in renal impairment
Explanation
Glyburide (glibenclamide) is metabolized in the liver to active metabolites that are renally excreted. In renal impairment these accumulate, causing prolonged and severe hypoglycemia. This is why glyburide is contraindicated when eGFR is below 60 mL/min. Glimepiride and gliclazide are safer alternatives in CKD because they produce inactive metabolites.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
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