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Thiopurinol: Dose-Related Effect on Urinary Oxypurine Excretion

  • R. Grahame
  • H. A. Simmonds
  • J. S. Cameron
  • A. Cadenhead
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 76B)

Abstract

Thiopurinol (mercapto-4-pyrazolo-(3,4-d)pyrimidine) has been shown to effectively reduce both plasma and urinary uric acid levels in the treatment of gout (2,4,5). These effects were observed without showing a concomitant increase in urinary hypoxanthine and xanthine excretion, (2,4,5). As an inhibitor of xanthine oxidase, thiopurinol has been shown to be only one tenth as active as allopurinol in vitro (3). Thiopurinol is ineffective in lowering uric acid levels in gout associated with a deficiency of the enzyme HGPRTase. This observation has led to the suggestion that the drug acts mainly by feedback inhibition of de novo purine synthesis; either by causing an alteration in the balance of available purine nucleotides or by the formation of thiopurinol ribotide (2,5). Extensive metabolic studies have recently been carried out in pigs using 14C allopurinol and 14C thiopurinol (7). These studies revealed no measurable tissue incorporation of either drug and showed that thiopurinol was less well absorbed than allopurinol when administered orally.

Keywords

Xanthine Oxidase Uric Acid Level Purine Metabolism Orotic Acid Xanthine Oxidase Activity 
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.

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References

  1. 1.
    Auscher, C., Mercier, No, Pasquier, C., and Delbarre, F., (1973), “Allopurinol and thiopurinol; effect on oxypurine excretion and on rate of in vitro synthesis of rlbunucleotides” purine Metabolism in Man, 41B, plenum press, 657–667Google Scholar
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    Delbarre, F., Auscher, C., De Gery, A., Brouilhet, Ho, and Olivier, L., (1968) “Le traitement de la dyspurinurie goutteuse par la mercapto-pyrazolo-pyrimidine. (M.P.P. Thiopurinol) presse Med 76 2329–2332Google Scholar
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    Grahame, R., Simmonds, H.A., Cadenhead, A., and Dean, B.M. (1974) “Metabolic Studies of Thiopurinol in man and the pig” Purine Metabolism in Man, 41B, Plenum Press, 597–605Google Scholar
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    Serre, H., Simon, L., and Claustre, J., (1970), “Les Urico-frenateurs dans le traitement de la goutte: A propos de 126 cas” Sem. Hop. paris. 46, 3295–3301.PubMedGoogle Scholar
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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • R. Grahame
    • 1
  • H. A. Simmonds
    • 1
  • J. S. Cameron
    • 1
  • A. Cadenhead
    • 1
  1. 1.Arthritis Research Unit and Department of MedicineGuy’s Hospital Medical schoolLondonUSA

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