Allopurinol and Other Inhibitors of Urate Synthesis

Relationship between plasma oxipurinol concentrations and xanthine oxidase activity in volunteers dosed with allopurinol.

“…No oxipurinol was produced in two such subjects when allopurinol was administkred. However, oxipurinol was measured in plasma in reasonable concentrations in two other subjects and it was suggested that the enzyme, aldehyde oxidase, which is very closely related to xanthine oxidase, was responsible for the metabolism of allopurinol in these individuals (Elion, 1978;Krenitsky et al, 1972). Thus, this enzyme may be responsible for the continued production of oxipurinol in the face of inhibition of xanthine oxidase induced by high doses of allopurinol.…”

“…Alternatively, the oxidation of allopurinol to oxipurinol may be inhibited only by relatively high concentrations of allopurinol and oxipurinol, when compared with other substrates such as xanthine and hypoxanthine. Thus, administration of allopurinol 50-100 mg kg'l intravenously was required to inhibit the oxidation of allopurinol to oxipurinol in dogs (Elion, 1978).…”

Management of Hyperuricemia and Gout

“…However, the dose of allopurinol should be adjusted upward suf fi cient to bring the serum urate levels to <6 mg/dl in order to prevent sodium urate crystal deposition. Both allopurinol and oxypurinol are relatively insoluble and may be deposited in the kidney parenchyma [ 24 ] .…”

Differentialindikation Urikosurika und Allopurinol

“…Urikosurika erh6hen jedoch die renale Clearance von Oxipurinol und vermindern dadurch den Allopurinoleffekt (Elion 1966(Elion , 1978. Dann, und nur dann ist es notwendig, A1lopurinol mit einem Ufikosurikum zu kombinieren.…”