A 22-year-old woman taking doxycycline for acne drinks two glasses of milk daily with each dose. She notices her acne has stopped responding. The reason for this therapeutic failure is:

• A Milk induces hepatic metabolism of doxycycline via CYP3A4
• B Calcium forms insoluble chelates with doxycycline, reducing gastrointestinal absorption ✓
• C Milk alkalinizes gastric pH, destroying the drug before absorption
• D Lactose competitively inhibits intestinal uptake transporters of tetracyclines

Explanation

Tetracyclines chelate divalent and trivalent cations such as calcium, magnesium, aluminium and iron, forming insoluble complexes that are poorly absorbed. Dairy products, antacids and iron supplements therefore markedly reduce bioavailability unless doses are separated by 2 to 3 hours. This is why tetracyclines are taken on an empty stomach with plenty of water. Hepatic enzyme induction does not explain failure, and gastric alkalinization is not the operative mechanism.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.