Advertisement

The Allopurinol Hypersensitivity Syndrome: Its Relation to Plasma Oxypurinol Levels

  • Esperanza Casas
  • Juan G. Puig
  • Felícitas A. Mateos
  • Manuel L. Jiménez
  • Alfredo D. Michán
  • Teresa H. Ramos
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 253A)

Abstract

Allopurinol (4-hydroxypyrazolo (3, 4-d)pyrimidine) is a potent inhibitor of uric acid synthesis commonly prescribed for the treatment of gout and other hyperuricemic states (1, 2). Most of the allopurinol is rapidly oxidized to oxypurinol, its major metabolic product (3), which in turn is a potent inhibitor of the enzyme xanthine oxydase. The half-clearance time of oxypurinol is far more prolonged than that of allopurinol (4). Hence, much of the inhibition of uric acid formation and possibly some adverse reactions ascribed to allopurinol may be due to oxypurinol. Pharmacologic studies have indicated that the serum concentration of oxypurinol may be related to the development of life-threatening allopurinol toxicity (5). Thus, it has been suggested that monitorization of plasma oxypurinol levels could prevent unwanted allopurinol effects (6). Recommended plasma oxypurinol concentrations are below 100 μM (7). In fact, no adverse reactions have been described with lower plasma oxypurinol concentrations (5–8). We describe a patient with a severe hypersensitivity reaction to allopurinol who had a plasma oxypurinol concentration of 50 μM.

Keywords

Uric Acid Serum Urate Cutaneous Rash Severe Hypersensitivity Reaction HPRT Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W.N. Kelley, and E.W. Holmes. Antihyperuricemic drugs. In: “Textbook of Rheumatology”, W.N. Kelley, E.D. Harris, S. Ruddy, and C.B. Sledge, ed., W.B. Saunders, Philadelphia, 857–870 (1985).Google Scholar
  2. 2.
    R.W. Rundles. The development of allopurinol. Arch Intern Med 145: 1492–1503 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    K.R. Hande, R. Eddie, and B. Chabner. Allopurinol kinetics. Clin Pharmacol Ther 23: 598–605 (1987).Google Scholar
  4. 4.
    G.B. Elion, T-F. Yü, A.B. Gutman, et al. Renal clearance of oxypurinol the chief metabolite of allopurinol. Am J Med 45: 69–77 (1968).PubMedCrossRefGoogle Scholar
  5. 5.
    G.B. Elion, F.M. Benezra, T.D. Beardmore, et al. Studies with allopurinol in patients with impaired renal function. Adv Exp Med Biol 122A: 263–267 (1980).PubMedGoogle Scholar
  6. 6.
    H.A. Simmonds, J.S. Cameron, G.S. Morris, et al. Allopurinol in renal failure and the tumour lysis syndrome. Clin Chim Acta 160: 189–195 (1986).PubMedCrossRefGoogle Scholar
  7. 7.
    K.R. Hande, R.M. Noone, and W.J. Stone. Severe allopurinol toxicity: Description and guidelines for prevention in patients with renal insufficiency. Am J Med 76: 47–56 (1984).PubMedCrossRefGoogle Scholar
  8. 8.
    J.S. Cameron, and H.A. Simmonds. Use and abuse of allopurinol. Br Med J 294: 1504–1505 (1987).CrossRefGoogle Scholar
  9. 9.
    H. Breithaupt, and G. Göbel. Determination of allopurinol and oxypurinol in biological fluids by HPLC. J Chromatogr 226: 237–242 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    I. Pascual-Castroviejo, A. Vélez, J.G. Puig, and M.L. Jiménez. Síndro-me de Lesch-Nyhan con déficit total de la enzima HPRT. Neurología 1: 44–45 (1986).PubMedGoogle Scholar
  11. 11.
    L. Hernández-Nieto, W.L. Nyhan, T. Page, et al. Síndrome de Lesch-Nyhan: nueva variante con actividad de hipoxantina-guanina fosforribo-sil transferasa (HGPRT) superior a la de la enfermedad clásica y de-tección del rasgo heterozigoto en los hematíes de la portadora. Med Clin (Barc) 84: 68–71 (1985).Google Scholar
  12. 12.
    A. Andrés, M. Praga, L.M. Ruilope, et al. Partial deficit of hypoxan-thine guanine phosphoribosyl transferase presenting as acute renal failure. Nephron 46: 179–181 (1987).PubMedCrossRefGoogle Scholar
  13. 13.
    G.P. Lupton, and R.B. Odom. The allopurinol hypersensitivity syndrome. J Am Acad Dermatol 1: 365–374 (1979).PubMedCrossRefGoogle Scholar
  14. 14.
    J.Z. Singer, and S.L. Wallace. The allopurinol hypersensitivity syndrome: unnecessary morbidity and mortality. Arthritis Rheum 29: 82–87 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    M.W. McKendrick, and A.M. Geddes. Allopurinol hypersensitivity. Br Med J 1: 988 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Esperanza Casas
    • 1
  • Juan G. Puig
    • 1
  • Felícitas A. Mateos
    • 1
  • Manuel L. Jiménez
    • 1
  • Alfredo D. Michán
    • 1
  • Teresa H. Ramos
    • 1
  1. 1.Departments of Internal Medicine and Clinical Biochemistry “La Paz” HospitalUniversidad AutónomaMadridSpain

Personalised recommendations