Drug breakdown: allopurinol

Day 1: 1950s cancer drug investigations led to the discovery of 6-mercaptopurine; the kinetics revealed the breakdown role of xanthine oxidase (XO). Further tests showed that an analogue to naturally occurring hypoxanthine, #allopurinol, could block XO and treat gout. It was approved in the US in 1966.

Day 2 (cont): #allopurinol is NOT used for acute gout; the initial decline of serum urate levels causes urate crystals to shed from cartilage into the joint space. Start #allopurinol after acute attack settled if indicated. If already taken when an attack happens, #allopurinol can be continued, with the attack managed separately.

Day 3: #allopurinol kinetics; good oral absorption and moderate volume of distribution, as concentrated in gut and liver. Liver breakdown releases active metabolite ‘oxypurinol’, also a xanthine oxidase inhibitor. Mainly renal elimination of metabolites; ~20% in faeces. T½ 1-2 hours.

Day 4: #allopurinol and active metabolite are xanthine oxidase inhibitors, which block the breakdown pathway of hypoxanthine>xanthine>uric acid. The reduced production of uric acid leads to lower serum levels; it can take a few months to lower uric acid levels as effective for prevention.