What is Allopurinol

What is Allopurinol? Allopurinol is an antipodagric drug that inhibits the synthesis of uric acid and its salts in the body. The drug has a specific ability to inhibit the enzyme xanthine oxidase, which is involved in the conversion of hypoxanthine into xanthine and xanthine into uric acid. As a consequence, the content of urates in the blood plasma is reduced and their deposition in the tissues and kidneys is prevented. Allopurinol is converted in the body to oxypurinol (alloxanthine), which also prevents the formation of uric acid, but the activity is inferior to allopurinol. 

Pharmacokinetics

After oral administration, allopurinol is absorbed quickly and completely. It is practically not absorbed in the stomach, absorption occurs in the duodenum and upper part of the small intestine. As a result of metabolism the main pharmacologically active metabolite is formed oxypurinol. Cmax of oxypurinol is reached after 3-4 hours, the rate of formation depends on the degree and rate of individual presystemic metabolism. Allopurinol and oxypurinol practically do not bind with plasma proteins. T½ of allopurinol from blood plasma is about 40 min, of oxypurinol — 17-21 h. 80% of allopurinol and oxypurinol are excreted by the kidneys, 20% — in the feces. In renal insufficiency T½ of oxypurinol increases.

Indications

  • Hyperuricemia (with serum uric acid levels of 500 μmol (8.5 mg/100 ml) or higher and not controlled by diet); 
  • Diseases caused by elevated levels of uric acid in the blood, especially in gout, urate nephropathy, and urate urolithiasis; 
  • Secondary hyperuricemia of various etiologies; 
  • Primary and secondary hyperuricemia in various hemoblastosis (acute leukemia, chronic myeloleukemia, lymphosarcoma); 
  • Cytostatic and radiation therapy for tumors; 
  • Psoriasis; 
  • Therapy with glucocorticosteroids.

Special indications 

The drug should be used by patients with renal insufficiency, as well as patients with disorders of hematopoiesis, under constant medical supervision. Use during pregnancy and lactation. Allopurinol administration during pregnancy is contraindicated. If it is necessary to use the drug during breast-feeding, breast-feeding must be discontinued.

Interactions 

The effectiveness of Allopurinol is reduced when using drugs with uricosuric action (sulfinpyrazone, probenecid and benzbromaron) and salicylates in high doses. Due to allopurinol’s ability to inhibit xanthine oxidase, the metabolism of purine derivatives such as azathioprine and mercaptopurine is slowed, so their usual dose should be reduced by 50-75%. Allopurinol in high doses slows down excretion of probenecid and inhibits theophylline metabolism. When concomitant use of Allopurinol with chlorpropamide the dose of chlorpropamide should be reduced. When concomitant use of Allopurinol with coumarin-type anticoagulants, their dose should be reduced, and blood clotting parameters should be monitored more frequently.