Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Allopurinol

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Allopurinol is a widely used drug in the management of hyperuricaemia. It is rapidly and extensively absorbed following oral administration. The major and active metabolite, oxypurinol, is detected in the circulation within 15 minutes of allopurinol administration. Oxypurinol concentrations are higher than those of the parent drug and accumulation occurs during long term administration. Up to 80% of allopurinol is recovered in the urine within 24 hours, mainly in the form of oxypurinol. Allopurinol is negligibly absorbed after rectal administration.

In animals, allopurinol is found in highest concentrations in vascular tissue, blood, liver, intestine and heart. It is negligibly bound to plasma proteins. Oxypurinol is eliminated by the kidney and has a much longer elimination half-life than allopurinol. Oxypurinol accumulates in patients with renal dysfunction; hence allopurinol dosages should be adjusted in such patients. Allopurinol inhibits the metabolism of 6-mercaptopurine and azathioprine, which require dosage modifications. The interaction of allopurinol with oral anticoagulants and phenytoin has not been clearly established in clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Appelbaum SJ, Mayersohn M, Dorr RT, Perrier D. Allopurinol kinetics and bioavailability. Intravenous, oral and rectal administration. Cancer Chemotherapy and Pharmacology 14: 789, 1982

    Google Scholar 

  • Benezra SA, Bennett TR. In Florey K (Ed.) Analytical profiles of drug substances, Vol. 7, pp. 1–17, Academic Press, New York, 1978

  • Berlinger WG, Park DG, Spector R. The effect of dietary protein on the clearance of allopurinol and oxypurinol. New England Journal of Medicine 313: 771–776, 1985

    Article  PubMed  CAS  Google Scholar 

  • Betz AL. Identification of hypoxanthine transport and xanthine oxidase activity in brain capillaries. Journal of Neurochemistry 44: 574–579, 1985

    Article  PubMed  CAS  Google Scholar 

  • Boston Collaborative Drug Surveillance Program. Allopurinol and cytotoxic drugs. Laboratory Investigation 227: 1036, 1974

    Google Scholar 

  • Caskey CT, Ashton DM, Wyngaarden JB. The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine nucleotides. Journal of Biological Chemistry 239: 2570–2579, 1964

    PubMed  CAS  Google Scholar 

  • Chang S, Kramer WG, Feldman S, Ballentine R, Frankel LS. Bioavailability of allopurinol oral and rectal dosage forms. International Journal of Clinical Pharmacology 38: 365–368, 1981

    CAS  Google Scholar 

  • Edwards NL, Recker D, Airozo D, Fox IH. Enhanced purine salvage during allopurinol therapy: an important pharmacologic property in humans. Journal of Laboratory and Clinical Medicine 98: 673–683, 1981

    PubMed  CAS  Google Scholar 

  • Elion GB, Benezra FM, Beardmore TD, Kelley WN. Studies with allopurinol in patients with impaired renal function. Advances in Experimental Biology and Medicine 1224: 263–267, 1980

    Article  Google Scholar 

  • Elion GB, Kovensky A, Hitchings GH, Metz E, Rundles RW. Metabolic studies of allopurinol, an inhibitor of xanthine oxidase. Biochemical Pharmacology 15: 836–880, 1966

    Article  Google Scholar 

  • Elion GB, Yu TF, Gutman GB, Hitchings GH. Renal clearance of oxypurinol, the chief metabolite of allopurinol. American Journal of Medicine 45: 69–77, 1968

    Article  PubMed  CAS  Google Scholar 

  • Endele R, Lettenbauer G. Hochdruckflussigchromatographische bestimmung von allopurinol und oxypurinol in serum. Journal of Chromatography 115: 228, 1975

    Article  PubMed  CAS  Google Scholar 

  • Glogner P, Heni N. Panztopenie nach kombinationsbehandlung mit allopurinol und azothioprin. Medizinische Welt 27: 1545, 1976

    PubMed  CAS  Google Scholar 

  • Hande KR, Chabner BA. A competitive protein binding assay for allopurinol and oxipurinol. Analytical Biochemistry 101: 26–33, 1980

    Article  PubMed  CAS  Google Scholar 

  • Hande KR, Noore RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for patients with renal insufficiency. American Journal of Medicine 76: 47–56, 1984

    Article  PubMed  CAS  Google Scholar 

  • Hande K, Reed E, Chabner B. Allopurinol kinetics. Clinical Pharmacology 23: 598–605, 1978

    CAS  Google Scholar 

  • Hornbeck CL, Floyd RA, Byfield JE, Griffiths JC, Frankel S, et al. Cerebrospinal fluid versus serum concentrations of 3-FU, allopurinol, and oxipurinol during treatment of metastatic brain cancer with 5-FU infusion, allopurinol, and radiation. Cancer Treatment Reports 66: 571–573, 1982

    PubMed  CAS  Google Scholar 

  • Jaeger VH, Russman D, Rasper J, Blome J. Vergleichende prufung der bioverfugbarkeit und des pharmakodynamischen effektes von funf allopurinol-zubereitungen. Arzneimittel-Forschung 32: 438–442, 1982

    PubMed  CAS  Google Scholar 

  • Jarasch ED, Grund C, Bruder G, Heid HW, Keenan TW, et al. Localisation of xanthine oxidase in mammary-gland epithelium and capillary endothelium. Cell 20: 67–82, 1981

    Article  Google Scholar 

  • Kelley WM, Beardmore TD. Allopurinol: alteration in pyrimidine metabolism in man. Science 169: 338–390, 1970

    Article  Google Scholar 

  • Kramer WG, Feldman S. Apparent metabolism of allopurinol by blood. Research Communications in Chemical Pathology and Pharmacology 18: 781–784, 1977

    PubMed  CAS  Google Scholar 

  • Marcus M, Tse FLS, Kleinberg SI. The bioavailability of two commercial preparations of allopurinol tablets. International Journal of Clinical Pharmacology 20: 302–305, 1982

    CAS  Google Scholar 

  • Mertz DP, Eichhorn R. Does benzbromarone in therapeutic doses raise renal excretion of oxipurinol? Klinische Wochenschrift 62: 1170–1172, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nelson DJ, Bugge CJL, Krasny HC, Elion GB. Formation of nucleotides of [614C]allopurinol and [614C]oxipurinol in rat tissues and effects on uridine nucleotide pool. Biochemical Pharmacology 22: 2003–2022, 1973

    Article  PubMed  CAS  Google Scholar 

  • Patel VS, Kramer WG. Allopurinol absorption from different sites of the rat gastrointestinal tract. Journal of Pharmaceutical Sciences 75: 275–277, 1986

    Article  PubMed  CAS  Google Scholar 

  • Petitpierre B, Perrin L, Rudhart M, Herrera A, Fabre J. Behaviour of chlorpropamide in renal insufficiency and under the effects of associated drug therapy. International Journal of Clinical Pharmacology 6: 120, 1972

    CAS  Google Scholar 

  • Ragab AH, Gilkerson E, Myers M. The effect of 6-mercaptopurine and allopurinol on granulopoiesis. Cancer Research 34: 2246, 1974

    PubMed  CAS  Google Scholar 

  • Rundles GH, Wyngaarden JB, Hutchings GH, Elion GB, Silberman HR. Effects of xanthine oxidase inhibition of thiopurine metabolism, hyperuricemia and gout. Transactions of Association of American Physicians 76: 126–140, 1963

    CAS  Google Scholar 

  • Simmonds HA, Levin B, Cameron JS. Variations in allopurinol metabolism by xanthinuric subjects. Clinical Science and Molecular Medicine 47: 173–178, 1974

    PubMed  CAS  Google Scholar 

  • Sved S, Wilson DL. Analysis of allopurinol and oxypurinol in plasma and its application to metabolic studies. Biopharmaceutics and Drug Disposition 1(3): 111–117, 1980

    Article  CAS  Google Scholar 

  • Sweetman L, Nyhan WL. Quantitation of oxypurines and allopurinol metabolites in biological fluids by cation exchange chromatography. Analytical Biochemistry 31: 358–365, 1969

    Article  PubMed  CAS  Google Scholar 

  • Vesell ES, Passananti GT, Greene EF. Impairment of drug metabolism in man by allopurinol and nortriptyline. New England Journal of Medicine 283: 1484, 1970

    Article  PubMed  CAS  Google Scholar 

  • Vogler WR, Bain JA, Huguley CM, Palmer HG, Lowrey ME. Metabolic and therapeutic effects of allopurinol in patients with leukaemia and gout. American Journal of Medicine 40: 548, 1966

    Article  Google Scholar 

  • Walter-Sack VI, Grobner W, Zollner N. Verlauf der oxipurinolspeigel im plasma nach akuter und chronischer gabe von allopurinol in verschiedenen zubereitunger. Arzneimittel-Forschung 29: 839–842, 1979

    PubMed  CAS  Google Scholar 

  • Wood MH, O’Sullivan WJ, Wilson M, Tiller DJ. Potentiation of an effect of allopurinol on pyrimidine metabolism by chlorothiazide in man. Clinical Experiments in Pharmacology and Physiology 1: 53, 1974

    Article  CAS  Google Scholar 

  • Yokochi K, Yokochi A, Chiba K, Ishizaki T. Phenytoin-allopurinol interaction: Michaelis-Menten kinetic parameters of phenytoin with and without allopurinol in a child with Lesch-Nyhan syndrome. Therapeutic Drug Monitoring 4: 353–357, 1982

    Article  PubMed  CAS  Google Scholar 

  • Young JL, Boswell RB, Nies AS. Severe allopurinol sensitivity: association with thiazides and prior renal compromise. Archives of Internal Medicine 134: 553, 1974

    Article  PubMed  Google Scholar 

  • Zimm S, Collins JM, O’Neill D, Chabner BA, Poplack DG. Inhibition of first pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clinical Pharmacology and Therapeutics 34: 810–817, 1983.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuffield Department of Orthopaedic Surgery and Medical Research Council Unit, University Department of Clinical Pharmacology, Oxford, England

    G. A. C. Murrell & W. G. Rapeport

Authors
  1. G. A. C. Murrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. G. Rapeport
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murrell, G.A.C., Rapeport, W.G. Clinical Pharmacokinetics of Allopurinol. Clin-Pharmacokinet 11, 343–353 (1986). https://doi.org/10.2165/00003088-198611050-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198611050-00001

Keywords

Search

Navigation