A 40-year-old man with acute lymphoblastic leukaemia on maintenance 6-mercaptopurine develops hyperuricaemia and is prescribed allopurinol. The oncologist simultaneously reduces the mercaptopurine dose. The reason is:

• A Allopurinol induces hepatic metabolism of mercaptopurine, lowering its levels
• B Xanthine oxidase degrades mercaptopurine, and its inhibition raises drug levels and marrow toxicity ✓
• C Both drugs compete for renal tubular secretion, raising plasma levels of both
• D Allopurinol displaces mercaptopurine from plasma protein binding sites

Explanation

6-Mercaptopurine is inactivated largely by xanthine oxidase via methylation-independent oxidative pathway to thiouric acid. Allopurinol blocks this route, so mercaptopurine levels rise sharply and fatal myelosuppression can occur unless the dose is cut to about one quarter. The interaction is metabolic, not renal or protein-binding related, and allopurinol decreases rather than increases degradation of the purine analogue.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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