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Allopurinol in the Treatment of Gout

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Article1 February 1966Allopurinol in the Treatment of GoutR. WAYNE RUNDLES, M.D., F.A.C.P., EARL N. METZ, M.D., H. R. SILBERMAN, M.D.R. WAYNE RUNDLES, M.D., F.A.C.P.Search for more papers by this author, EARL N. METZ, M.D.Search for more papers by this author, H. R. SILBERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-2-229 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAllopurinol, 4-hydroxypyrazolo (3,4-d) pyrimidine (4-HPP),*recently introduced as a new type of agent useful in the treatment of gout, developed from studies undertaken to increase the therapeutic efficacy of 6-mercaptopurine (6-MP) and related thiopurines in leukemia. Since the biologically active form of 6-MP is its ribonucleotide (Figure 1) (1-4), all reactions leading to the removal of 6-MP from this anabolic pathway would decrease its activity. Studies on the metabolic fate of 6-MP in the mouse (5) and the human (6-9) have shown that the major catabolic pathway is oxidative. About 25 to 30% of the total dose of 6-MP is...References1. WAYPARKS JLRE: Enzymatic synthesis of 5′-phosphate nucleotides of purine analogues. J. Biol. Chem. 231: 467, 1958. CrossrefMedlineGoogle Scholar2. SALSERHUTCHINSONBALIS JSDJME: Studies on the mechanism of action of 6mercaptopurine in cell-free preparations. J. Biol. Chem. 235: 429, 1960. CrossrefMedlineGoogle Scholar3. PATERSON AR: Thiopurine nucleotide synthesis in a 6-MP-resistant subline of the Ehrlich ascites carcinoma and growth inhibition by certain antimetabolites. Canad. J. Biochem. 38: 1129, 1960. MedlineGoogle Scholar4. BROCKMAN RW: A mechanism of resistance to 6-mercaptopurine: metabolism of hypoxanthine and 6-mercaptopurine by sensitive and resistant neoplasms. Cancer Res. 20: 643, 1960. MedlineGoogle Scholar5. ELIONBIEBERHITCHINGS GBSGH: The fate of 6-mercaptopurine in mice. Ann. N. Y. Acad. Sci. 60: 297, 1954. CrossrefMedlineGoogle Scholar6. HAMILTONELION LGB: The fate of 6-mercaptopurine in man. Ibid., p. 304. Google Scholar7. ELIONCALLAHANHITCHINGSRUNDLES GBSWGHRW: Relationship between drug metabolism and antitumor effects of thiopurines in mouse and man, in Proceedings of the VIIIth International Congress of Hematology. Pan Pacific Press, Tokyo, 1960, p. 642. Google Scholar8. ELIONCALLAHANHITCHINGSRUNDLESLASZLO GBSWGHRWJ: Experimental, clinical, and metabolic studies of thiopurines, in Cancer Chemother. Rep. No. 16. February, 1962, p. 197. Google Scholar9. ELIONCALLAHANRUNDLESHITCHINGS GBSWRWGH: Relationship between metabolic fates and antitumor activities of thiopurines. Cancer Res. 23: 1207, 1963. MedlineGoogle Scholar10. ELIONMUELLERHITCHINGS GBSGH: Studies on condensed pyrimidine systems. XXI. The isolation and synthesis of 6-mercapto-2,8-purinediol (6-thiouric acid). J. Amer. Chem. Soc. 81: 3042, 1959. CrossrefGoogle Scholar11. SILBERMANWYNGAARDEN HRJB: 6-Mercaptopurine as substrate and inhibitor of xanthine oxidase. Biochim. Biophys. Acta 47: 178, 1961. CrossrefGoogle Scholar12. ELIONCALLAHANNATHANBIEBERRUNDLESHITCHINGS GBSWHSRWGH: Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem. Pharmacol. 12: 85, 1963. CrossrefGoogle Scholar13. FEIGELSONDAVIDSONROBINS PJDRK: Pyrazolopyrimidines as inhibitors and substrates of xanthine oxidase. J. Biol. Chem. 226: 993, 1957. CrossrefMedlineGoogle Scholar14. ELIONTAYLORHITCHINGS GBTJGH: Binding of substrates and inhibitors to xanthine oxidases from different species (abstract). VI Intl. Cong. Biochem. Abstracts IV: 305, 1964. Google Scholar15. SKIPPERROBINSTHOMSONCHENGBROCKMANSCHABEL HERKJRCCRWFM: Structure-activity relationships observed on screening a series of pyrazolopyrimidines against experimental neoplasms. Cancer Res. 17: 579, 1957. MedlineGoogle Scholar16. RUNDLESSILBERMANHITCHINGSELION RWHRGHGB: Effects of xanthine oxidase inhibitor on clinical manifestations and purine metabolism in gout (abstract). Ann. Intern. Med. 60: 717, 1964. LinkGoogle Scholar17. HITCHINGS GH: Summary of informal discussion on the role of purine antagonists. Cancer Res. 23: 1218, 1963. MedlineGoogle Scholar18. RUNDLESWYNGAARDENHITCHINGSELIONSILBERMAN RWJBGHGBHR: Effects of xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout. Trans. Assoc. Amer. Physicians 76: 126, 1963. Google Scholar19. CARTWRIGHT GE: Diagnostic Laboratory Hematology, 3rd ed. Grune & Stratton, Inc., New York, 1963. Google Scholar20. LIDDLESEEGMILLERLASTER LJEL: The enzymatic spectrophotometric method for determination of uric acid. J. Lab. Clin. Med. 54: 903, 1959. MedlineGoogle Scholar21. KLINENBERGGOLDFINGERSEEGMILLER JRSEJE: The effectiveness of the xanthine oxidase inhibitor allopurinol in the treatment of gout. Ann. Intern. Med. 62: 639, 1965. LinkGoogle Scholar22. MAZURGREENSAHACARLETON ASAA: Mechanism of release of ferritin iron in vivo by xanthine oxidase. J. Clin. Invest. 37: 1809, 1958. CrossrefMedlineGoogle Scholar23. AYVAZIAN JH: Xanthinuria and hemochromatosis. New Eng. J. Med. 270: 18, 1964. CrossrefMedlineGoogle Scholar24. Editorial: Xanthine oxidase and hemochromatosis. Ibid., p. 53. Google Scholar25. CROSBY WH: Letter to the Editor. Ibid., p. 535. Google Scholar26. FISCHERPRICE DSDC: A simple serum iron method using the new sensitive chromogen tripyridyl-s-triazine. Clin. Chem. 10: 21: 1964. CrossrefMedlineGoogle Scholar27. PRICECOHNWASSERMANREIZENSTEINCRONKITE DCSHLRPGEP: The determination of iron absorption and loss by whole body counting. Blood 20: 517, 1962. CrossrefMedlineGoogle Scholar28. ELIONHITCHINGS GBGH: Personal communication. Google Scholar29. HAYESMETZROBINSONRUNDLES CPENRRRW: The use of allopurinol (HPP) to control hyperuricemia in patients on chronic intermittent hemodialysis. Trans. Amer. Soc. Artif. Intern. Organs. 11: 247, 1965. CrossrefMedlineGoogle Scholar30. YÜGUTMAN TAB: Effect of allopurinol (4-hydroxypyrazolo (3,4-d) pyrimidine) on serum and urinary uric acid in primary and secondary gout. Amer. J. Med. 37: 885, 1964. CrossrefMedlineGoogle Scholar31. HALLHOLLOWAYSCOTT APVPJT: 4-hydroxypyrazolo (3,4-d) pyrimidine (HPP) in the treatment of gout. Preliminary observations. Amer. Rheum. Dis. 23: 439, 1964. CrossrefMedlineGoogle Scholar32. STETTENSEEGMILLERLASTERSOKOLOFFBUNIMWYNGAARDEN DJELLJJJB: Metabolic and clinical aspects of gout. Amer. J. Med. 22: 807, 1957. CrossrefMedlineGoogle Scholar33. TALBOT JH: Gout, 2nd ed. Grune & Stratton, Inc., New York, 1964. Google Scholar34. GUTMAN AB: Significance of the renal clearance of uric acid in normal and gouty man. Amer. J. Med. 37: 833, 1964. CrossrefMedlineGoogle Scholar35. KAPLANBERNSTEINWALLACEHALBERSTAM DDSLD: Serum and urinary amino acids in normouricemic and hyperuricemic subjects. Ann. Intern. Med. 62: 658, 1965. LinkGoogle Scholar36. MCCARTYHOLLANDER DJJL: Identification of urate crystals in gouty synovial fluid. Ann. Intern. Med. 54: 452, 1961. LinkGoogle Scholar37. SEEGMILLERHOWELLMALAWISTA JERRSE: The inflammatory reaction to sodium urate. Its possible relationship to the genesis of acute gouty arthritis. JAMA 180: 469, 1962. Google Scholar38. MALAWISTASEEGMILLER SEJE: The effect of pretreatment with colchicine on the inflammatory response to microcrystalline urate: a model for gouty inflammation. Ann. Intern. Med. 62: 648, 1965. LinkGoogle Scholar39. WYNGAARDENRUNDLESMETZ JBRWEN: Allopurinol in the treatment of gout (editorial). Ibid., p. 842. Google Scholar40. GONICKRUBINIGLEASONSOMMERS HCMEIOSC: The renal lesion in gout. Ibid., p. 667. Google Scholar41. DICKINSONSMELLIE CJJM: Xanthinuria. Brit. Med. J. 2: 1217, 1959. CrossrefMedlineGoogle Scholar42. GOLDFINGERKLINENBERGSEEGMILLER SJRJE: The renal excretion of oxypurines. J. Clin. Invest. 44: 623, 1965. CrossrefMedlineGoogle Scholar43. WYNGAARDENASHTON JBDM: The regulation of activity of phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides: a potential feedback control of purine biosynthesis. J. Biol. Chem. 234: 1492, 1959. CrossrefMedlineGoogle Scholar44. 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 Scholar45. POMALESELIONHITCHINGS RGBGH: Xanthine as a precursor of nucleic acid purines in the mouse. Biochim. Biophys. Acta 95: 515, 1965. CrossrefMedlineGoogle Scholar46. ENGELMANWATTSKLINENBERGSJOERDSMASEEGMILLER KRWJRAJE: Clinical, physiological and biochemical studies of a patient with xanthinuria and pheochromocytoma. Amer. J. Med. 37: 839, 1964. CrossrefMedlineGoogle Scholar47. WHITEHANDLERSMITH APEL: Principles of Biochemistry, 3rd ed. McGraw-Hill Book Co., New York, 1964. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Durham, North CarolinaFrom the Hematology Laboratory, Duke Hospital, and the Department of Medicine, Duke University School of Medicine, Durham, N. C.This study was undertaken as an exploratory trial for the Southeastern Cancer Chemotherapy Cooperative Study Group. The work was supported in part by grant CY-3177 from the National Cancer Institute, Cancer Chemotherapy National Service Center, Bethesda, Md., and grant MO1-FR-30 from the National Institutes of Health supporting the Duke Medical Center Clinical Research Unit.Dr. Metz was a Trainee in Cancer Chemotherapy and Hematology supported by grant T4 CA 5042 from the National Cancer Institute.Requests for reprints should be addressed to R. Wayne Rundles, M.D., Department of Medicine, Duke University Medical Center, Durham, N. C. 27706.*Zyloprim®, Burroughs Wellcome 56-158. 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Uric Acid and Arteriosclerosis in Apolipoprotein E-Deficient MiceGicht ist mehr als nur PodagraUnderstanding the dose-response relationship of allopurinol: predicting the optimal dosageAllopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012The population pharmacokinetics of allopurinol and oxypurinol in patients with goutAntihyperuricemic AgentsThe Rheumatology of GoutA Case of Gingival Ulcer Thought to Be Caused by AllopurinolBis[5-oxo-4,5-dihydro-8 H -2-azonia-4,8,9-trizabicyclo[4.3.0]nona-2,6,9(1)-triene] sulfateGout management: Let's get it right this timeEffects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trialFebuxostat, a novel drug for the treatment of hyperuricemia of goutGold salts, D-penicillamine and allopurinolLowering serum uric acid levels: What is the optimal target for improving clinical outcomes in gout?Clinical Trials in Crystal ArthropathyTreatment of Crystal Arthropathy—History and AdvancesManagement of Acute and Chronic Gouty ArthritisDiuretic and Uricosuric AgentsGold salts, D-penicillamine and allopurinolGout: diet and uric acid revisitedEfficacy and safety of desensitization to allopurinol following cutaneous reactionsNucleobase transportersFormulation Development of Allopurinol Suppositories and InjectablesNephrotoxicity of gold salts, D-penicillamine, and allopurinolClinical investigators as critical determinants in pharmaceutical innovationThe pharmacokinetics of oral and intravenous allopurinol and intravenous oxypurinol in the horseAllopurinol-induced toxic pustulodermaDesensitization to allopurinol in patients with gout and cutaneous reactionsPolycythemia veraPediatric Neoplastic DisordersGout and HyperuricemiaCrystal-associated arthropathiesWann behandelt man die Hyperurikämie?Wahl der Medikamente, Dosierung, ErfolgskontrolleThe purine path to chemotherapyControl of Crystal-Induced ArthropathiesDer Purin-Weg zur Chemotherapie (Nobel-Vortrag)The Purine Path to ChemotherapyThe purine path to chemotherapyTherapy in GoutA study of dose-response relationships of allpurinol in the presence of low or high purine turnoverEffect of allopurinol on the first-pass metabolism of 6-mercaptopurine in the ratThe Mackerel was in Fact a Red HerringHyperuricemia and GoutThe allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortalityWhen to Treat HyperuricaemiaAllopurinol hypersensitivity syndrome as a cause of hepatic fibrin-ring granulomasAllopurinol hypersensitivity in a patient with severe, chronic, tophaceous goutGoutALLOPURINOL HYPERSENSITIVITY: A POTENTIALLY LIFE THREATENING REACTIONFULMINANT HEPATIC FAILURE DUE TO ALLOPURINOLMetabolic Studies of High Doses of Allopurinol in HumansDrug therapy (3): ‘specific’ drugsProceedings of a symposium on crystal-related arthropathies. 22 October and 23 October, 1982, Bristol Polytechnic, Bristol.Gout with apparent resistance to allopurinolAllopurinol Hepatotoxicity Report of Two Cases and Review of the LiteratureF. H. AL-KAWAS, M.D., L. B. SEEFF, M.D., R. A. BERENDSON, M.D., H. J. ZIMMERMAN, M.D., K. G. ISHAK, M.D.Determination of allopurinol and oxipurinol in biological fluids by high-performance liquid chromatographyAcute adverse reactions attributed to allopurinol in hospitalised patients.Bullae Associated with AllopurinolIntensivmedizinA competitive protein binding assay for allopurinol and oxipurinolThe allopurinol hypersensitivity syndromeAllopurinol HypersensitivityControl of Hyperuricemia"ALLOPURINOL-TYPE" RASH DUE TO BUSULPHANUNEVEN GEOGRAPHICAL DISTRIBUTION OF 15;17-TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKÆMIAX-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: Effects of oral allopurinol and adenylateKomplikationen und supportive Therapie der Leukämien und malignen Non-Hodgkin-LymphomeDie chronische myeloische LeukämieAllopurinol and Other Inhibitors of Urate SynthesisAllopurinol hepatotoxicityAllopurinol Associated Hypersensitivity Reactions: Cutaneous and Renal ManifestationsAllergic Reaction to Allopurinol with Cross-Reactivity to OxypurinolO. LOCKARD Jr., M.D., C. HARMON, M.D., K. NOLPH, M.D., W. IRVIN, M.D.Allopurinol hypersensitivityDauertherapieUric Acid Metabolism in ManHypouricemiaThe influence of allopurinol on renal function in goutZur Beeinflussung der Purin- und Pyrimidinsynthese durch AllopurinolThe Leukemias and LymphomasLOCAL IMMUNITY AND ULCERATIVE COLITISALLOPURINOL AND BONE-MARROW DEPRESSIONEffects of Allopurinol and Oxipurinol on Pyrimidine Biosynthesis in ManContributo Allo Studio Della Litolisi Vescicale in Varie Condizioni SperimentaliMetabolic studies of purine metabolism in the pig during the oral administration of guanine and allopurinolEFFECTS OF CARBON, NITROGEN, AND ALLOPURINOL ON THE ABUNDANCE OF PARTICIPATE INCLUSIONS IN A MARINE DINOFLAGELLATE12The Spectrum of Myeloproliferative DisordersAplastic agranulocytosis after allopurinol therapyLa Terapia Medica Della Calcolosi Urica UrinariaHazard of Combining Allopurinol and ThiopurineTHE MANAGEMENT OF GOUTGranulomatous Hepatitis in a Patient Receiving AllopurinolALLOPURINOL AND OXIPURINOL: ALTERATION OF PURINE AND PYRIMIDINE METABOLISM IN CELL CULTUREL'Allopurinolo in Urologia Nota 2 A : La Calcolosi UricaThe effect of allopurinol on the excretion of oxypurines by the chickThe myeloproliferative disordersHyperuricemia Complicating Acute LeukemiaThe Dias Rounds Drug Information Analysis ServiceDisorder of purine metabolism due to partial deficiency of hypoxanthine-guanine phosphoribosyltransferaseVasculitis with allopurinol therapyNucleotide Biosynthesis from Preformed Purines in Mammalian Cells: Regulatory Mechanisms and Biological SignificancePhysiologic and Biochemical Basis for the Treatment of Gout and HyperuricemiaUric Acid Renal Lithiasis: Management by AllopurinolHypoxanthine-Guanine Phosphoribosyltransferase Deficiency in GoutWILLIAM N. KELLEY, M.D., MARTIN L. GREENE, M.D., FREDERICK M. ROSENBLOOM, M.D., J. FRANK HENDERSON, PH.D., J. E. SEEGMILLER, M.D.L'Allopurinolo in Urologia(*): Nota 1aUric acid nephrolithiasisRenal clearance of oxipurinol, the chief metabolite of allopurinolETIOLOGY AND TREATMENT OF GOUT-MODERN CONCEPTSChronic allopurinol administration and iron storage in miceSulla Prevenzione Delle Calcolosi Da Acido Urico Con AllopurinoloAn Enzymatic Basis for Variation in Response to AllopurinolKompetitive Enzymmechanismen bei der Therapie von Hämoblastosen mit AntimetabolitenHERPES SIMPLEX IN PEPTIC ULCERATION?ALLOPURINOL AND IRON STORAGEACADEMIC RADIOLOGY AND RECRUITMENTALLOPURINOL AND IRON METABOLISMTHE USE OF THE XANTHINE OXIDASE INHIBITOR, ALLOPURINOL, IN THE CONTROL OF HYPERURICAEMIA, GOUT AND URIC ACID CALCULIStudies of uric acid metabolism in glycogen storage disease associated with gouty arthritisAllopurinol Control of Hyperuricosuria: A New Concept in the Prevention of Uric Acid StonesASPIRIN AND PLATELET STICKINESSALLOPURINOL AND IRON METABOLISMRecent Advances in the Rheumatic DiseasesEPHRAIM P. ENGLEMAN, M.D., F.A.C.P., MARTIN A. SHEARN, M.D., F.A.C.P.Use of allopurinol in preventing hyperuricemia in leukemia and lymphomaMetabolic Changes Associated with Recovery from Vitamin B12 DeficiencyEFFECT OF A XANTHINE-OXIDASE INHIBITOR (ALLOPURINOL) ON RADIOIRON ABSORPTION IN MANTHE KIDNEY IN HEPATIC DISEASE AND IN GOUT: CLINICAL AND PATHOLOGIC ASPECTS 1 February 1966Volume 64, Issue 2Page: 229-258KeywordsAllopurinolArthritisCancer chemotherapyExcretionGoutHematology and oncologyHospital medicineResearch laboratoriesToxicityUric acid ePublished: 1 December 2008 Issue Published: 1 February 1966 Copyright & PermissionsCopyright ©, 1966, by The American College of PhysiciansPDF downloadLoading ...

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