Allopurinol is a xanthine oxidase inhibitor used to reduce urinary and serum uric acid concentrations in patients with gout, recurrent calcium oxalate calculi, and various malignancies. Allopurinol administration can be in two forms, either oral or intravenous (IV). While oral administration is the standard route for gout and uric acid or calcium oxalate nephrolithiasis, IV allopurinol is for the prevention of tumor lysis syndrome and management of cancer therapy-induced hyperuricemia in patients who cannot tolerate oral therapy. Allopurinol is a structural analog of the natural purine base, hypoxanthine. After ingestion, allopurinol is metabolized to its active metabolite, oxypurinol in the liver, which acts as an inhibitor of xanthine oxidase enzyme. Xanthine oxidase is an enzyme involved in purine metabolism. Adenosine is a purine which is converted to adenosine by the enzyme purine nucleoside phosphorylase. Adenosine is then converted to inosine via the enzyme adenosine deaminase. Hypoxanthine is formed from inosine using the enzyme purine nucleoside phosphorylase. Hypoxanthine then forms xanthine through xanthine oxidase. Guanine, another purine found in the body, can be converted to xanthine by the enzyme guanine deaminase. The xanthine formed from these purines go on the form uric acid using the enzyme xanthine oxidase. Allopurinol and its active metabolite inhibit xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. This drug increases the reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis by a process that involves the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). This process results in an increased nucleotide concentration, which causes feedback inhibition of de novo purine synthesis. The end result is decreased urine and serum uric acid concentrations, which decreases the incidence of gout symptoms.

Allopurinol Pathway (New) References