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Use of Polyethylene Glycol-Modified Uricase (PEG-Uricase) to Treat Hyperuricemia in a Patient with Non-Hodgkin Lymphoma

Cynthia C. Chua, MD; Michael L. Greenberg, PhD; Anna T. Viau, PhD; Mary Nucci, MS; Wayne D. Brenckman Jr., MD; and Michael S. Hershfleld, MD
[+] Article, Author, and Disclosure Information

Grant Support: Partial funding by National Institutes of Health grant DK20902 to Dr. Hershfield and Small Business Innovative Research (SBIR) grant AM37751 to Enzon, Inc. Dr. Chua is the recipient of a fellowship from the Leukemia Society of America.

Requests for Reprints: Michael S. Hershfield, MD, Box 3049, Duke University Medical Center, Durham, NC 27710.

Current Author Addresses: Dr. Chua: Department of Medicine. Dr. Greenberg: Department of Medicine, Division of Rheumatology and Oncology. Dr. Brenckman: Department of Medicine, Division of Hematology-Oncology. Dr. Hershfield: Department of Medicine, Division of Rheumatology and Immunology, and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710.

Dr. Viau and Ms. Nucci: Enzon Inc., South Plainfield, NJ 07080.

© 1988 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1988;109(2):114-117. doi:10.7326/0003-4819-109-2-114
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Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 µmol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 µmol/L (9 mg/ dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.





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