The Effectiveness of the Xanthine Oxidase Inhibitor Allopurinol in the Treatment of Gout
Authors: JAMES R. KLINENBERG
Journal: Annals of Internal Medicine (1965)

Article1 April 1965The Effectiveness of the Xanthine Oxidase Inhibitor Allopurinol in the Treatment of GoutJAMES R. KLINENBERG, M.D., STEPHEN E. GOLDFINGER, M.D., J. EDWIN SEEGMILLER, M.D.JAMES R. KLINENBERG, M.D., STEPHEN E. GOLDFINGER, M.D., J. EDWIN SEEGMILLER, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-4-639 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe clinical benefits derived from controlling the hyperuricemia of patients with gouty arthritis have been well-established (1, 2). This has been achieved by using uricosuric drugs to increase the renal excretion of uric acid, thereby lowering the serum urate concentration. Since the majority of patients with gout have evidence of some degree of overproduction of uric acid (3), another rational approach to therapy would be to decrease uric acid production. A decrease in purine biosynthesis in the human has been produced by the administration of the glutamine analogues 6-diazo-5 oxo-L-norleucine (DON) (4) and azaserine (5), which block an early stage...References1. YUGUTMAN TFAB: Mobilization of gouty tophi by protracted use of uricosuric agents. Amer. J. Med. 11: 765, 1951. CrossrefMedlineGoogle Scholar2. BARTELSMATOSSIAN ECGS: Gout: six-year follow-up on probenecid (Benemid) therapy. Arthritis Rheum. 2: 193, 1959. CrossrefMedlineGoogle Scholar3. SEEGMILLERGRAYZELLASTERLIDDLE JEAILL: Uric acid production in gout. J. Clin. Invest. 40: 1304, 1961. CrossrefMedlineGoogle Scholar4. GRAYZELSEEGMILLERLOVE AIJEE: Suppression of uric acid synthesis in the gouty human by the use of 6-diazo-5-oxo-L-norleucine. J. Clin. Invest. 39: 447, 1960. CrossrefMedlineGoogle Scholar5. ZUCKERMANDRELLLEVIN RWMH: The effect of azaserine on the incorporation of glycine-C14 into uric acid in the gouty human (abstract). Ninth International Congress on Rheumatic Diseases, Toronto, 1957, Vol. II, p. 204. Google Scholar6. LORZHITCHINGS DCGH: Specificity of xanthine oxidase. Fed. Proc. 9: 197, 1950. Google Scholar7. FIEGELSONDAVIDSONROBINS PJDRK: Pyrazolopyrimidines as inhibtors and substrates of xanthine oxidase. J. Biol. Chem. 226: 993, 1957. CrossrefMedlineGoogle Scholar8. ELIONTAYLORHITCHINGS GBTJGH: Binding of substrates and inhibitors to xanthine oxidases from different species (abstract). VI International Congress of Biochemistry, New York, 1964, p. IV-42. Google Scholar9. WATTSWATTSSEEGMILLER RWJEJE: Radiochemical determination of xanthine oxidase activity in human tissues and its inhibition by 4-hydroxypyrazolo (3,4-d) pyrimidine. In preparation. Google Scholar10. KLINENBERGGOLDFINGERMILLERSEEGMILLER JRSJJE: The effectiveness of a xanthine oxidase inhibitor in the treatment of gout (abstract). Arthritis Rheum. 6: 779, 1963. Google Scholar11. WATTSENGELMANKLINENBERGSJOERDSMASEEGMILLER RWKJAJE: Enzyme defect in a case of xanthinuria. Nature (London) 201: 395, 1964. CrossrefMedlineGoogle Scholar12. WYNGAARDENSEEGMILLERLASTERBLAIR JBJELAE: Utilization of hypoxanthine, adenine and 4-amino-5-imidazolecarboxamide for uric acid synthesis in man. Metabolism 8: 455, 1959. MedlineGoogle Scholar13. SEEGMILLERGRAYZELHOWELLPLATO JEAIRRC: Renal excretion of uric acid in gout. J. Clin. Invest. 41: 1094, 1962. CrossrefMedlineGoogle Scholar14. LIDDLESEEGMILLERLASTER LJEL: Enzymatic spectrophotometric method for deermination of uric acid. J. Lab. Clin. Med. 54: 903, 1959. MedlineGoogle Scholar15. KLINENBERGGOLDFINGERBRADLEYSEEGMILLER JSKJE: An enzymatic spectrophotometric method for the determination of hypoxanthine and xanthine. In preparation. Google Scholar16. GOLDFINGERKLINENBERGSEEGMILLER SEJRJE: The renal clearance of oxypurines. J. Clin. Invest. In press. Google Scholar17. ELIONCALLAHANNATHANBIEBERRUNDLESHITCHINGS GBSHSRWGH: Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem. Pharmacol. 12: 85, 1963. CrossrefGoogle Scholar18. RUNDLESWYNGAARDENHITCHINGSELIONSILBERMAN RWJBGHGBHR: Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout. Trans. Ass. Amer. Physicians 76: 126, 1963. Google Scholar19. POMALESBIEBERFRIEDMANHITCHINGS RSRGH: Augmentation of the incorporation of hypoxanthine into nucleic acids by the administration of an inhibitor of xanthine oxidase. Biochim. Biophys. Acta 72: 119, 1963. CrossrefMedlineGoogle Scholar20. YÜGUTMAN TFAB: Effect of allopurinol (4-hydroxypyrazolo-(3,4d) pyrimidine) on serum and urinary uric acid in primary and secondary gout. Amer. J. Med. 37: 885, 1964. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, MarylandFrom the Arthritis and Rheumatism Branch, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Md.Requests for reprints should be addressed to J. E. Seegmiller, M.D., National Institute of Arthritis and Metabolic Diseases, Clinical Center, Bethesda, Md. 20014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDietary supplements for chronic goutAcute Tumor Lysis Syndrome: A Metabolic Emergency in Cancer PatientsFebuxostat-based amides and some derived heterocycles targeting xanthine oxidase and COX inhibition. 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KELLEY, M.D., MARTIN L. GREENE, M.D., FREDERICK M. ROSENBLOOM, M.D., J. FRANK HENDERSON, PH.D., J. E. SEEGMILLER, M.D.Long-Term Treatment of Gout with "Allopurinol"Xanthine stone formationBiologically Active PyraaolesChronic allopurinol administration and iron storage in miceSulla Prevenzione Delle Calcolosi Da Acido Urico Con AllopurinoloAn Enzymatic Basis for Variation in Response to AllopurinolInhibition of aminonucleoside nephrosis in ratsTHE USE OF THE XANTHINE OXIDASE INHIBITOR, ALLOPURINOL, IN THE CONTROL OF HYPERURICAEMIA, GOUT AND URIC ACID CALCULIA method for the determination of xanthine and hypoxanthine in biological fluidsAllopurinol in the treatment of uraemic patients with gout.Treatment of Uric Acid Urolithiasis With Allopurinol: A Xanthine Oxidase InhibitorMetabolism of Oxypurines In ManMetabolic Changes Associated with Recovery from Vitamin B12 DeficiencyMetabolic studies of allopurinol, an inhibitor of xanthine oxidaseMetabolic and therapeutic effects of allopurinol in patients with leukemia and goutSymposium on Gout and other Disorders of Purine MetabolismUse of Allopurinol for Prevention and Control of Hyperuricemia in Patients with Neoplastic DiseaseAllopurinol in the Treatment of GoutR. WAYNE RUNDLES, M.D., F.A.C.P., EARL N. METZ, M.D., H. R. SILBERMAN, M.D.The effectiveness of allopurinol in the treatment of goutArthritis—The Great CripplerGout 1 April 1965Volume 62, Issue 4Page: 639-647KeywordsAllopurinolArthritisAttentionDrugsExcretionGlutamineGoutMetabolic disordersPurinesUric acid Issue Published: 1 April 1965 CopyrightCopyright, ©, 1965, by The American College of PhysiciansPDF DownloadLoading ...