Reduction of Plasma Urate Levels in the Cockerel with

Abuchowskl, Abraham, Dennis Karp and Frank F. Davis: injection, whereas 1 0 U were effective for less than 6 hr. After Reduction of plasma urate levels in the cockerel with polyeth- injection with four-weekly doses of enzyme, unmodified uricase ylene glycol-uricase. J. Pharmacol. Exp. Ther. 21 9: 352-354, was ineffective in lowering plasma urate levels. Polyethylene 1 981. glycol-uricase, however, was as effective as on the first injec-tion. Both enzyme preparations appear in the lymph shortly Uricase from C. utilis and uricase to which polyethylene glycol after injection into the rat, although polyethylene glycol-uricase had been aftached were injected into leghorn cockerels in an appears slightly sooner and maintains a more constant level attempt to lower plasma urate levels. Twenty units of either than uricase. enzyme reduced urate levels to near zero for 24 hr on initial Uricase (urate oxidase; EC 1.7.3.3) is absent in man and as a for hyperuricemia, especially acute hyperuricemia involving result uric acid is the end product of purine metabolism. This renal insufficiency. causes the human species to have a higher serum urate concen- This paper describes the in vivo efficacy of PEG-uricase in tration than other mammals and increases the susceptibility of lowering blood urate levels in leghorn cockerels. The ability of man to hyperuricemia and gout (Wyngaarden and Kelly, 1976). PEG-uricase to enter the lymph system also is described. Treatment of these disorders generally involves drugs which decrease synthesis or increase elimination of uric acid. Unfor- Methods tunately, the drugs presently in use, such as colchicine, proben-C. Utilis uricase was a gift from Toyobo Company, Ltd. (Osaka, ecid and allopurinol, all cause side effects of varying severity Japan. Uric acid was obtained from Fisher Scientific Company (Pitts