A 58-year-old man with type 2 diabetes on glibenclamide develops severe hypoglycemia after starting trimethoprim-sulfamethoxazole for a urinary tract interaction. The drug interaction occurs because sulfonamides:
- A Increase renal tubular reabsorption of glibenclamide
- B Stimulate pancreatic insulin secretion synergistically
- C Inhibit CYP2C9 metabolism of glibenclamide and displace it from protein binding ✓
- D Compete with glibenclamide for biliary excretion
Correct answer: C. Inhibit CYP2C9 metabolism of glibenclamide and displace it from protein binding
Explanation
Sulfonamides like trimethoprim-sulfamethoxazole inhibit CYP2A9, the main enzyme metabolizing sulfonylureas such as glibenclamide (glyburide). They also displace sulfonylureas from plasma protein binding, increasing free drug concentration. This dual interaction significantly raises hypoglycemia risk. Glibenclamide is the most CYP2A9-dependent sulfonylurea, making it most susceptible.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
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