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Clinical Pharmacokinetics

, Volume 46, Issue 8, pp 623–644 | Cite as

Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol

  • Richard O. Day
  • Garry G. Graham
  • Mark Hicks
  • Andrew J. McLachlan
  • Sophie L. Stocker
  • Kenneth M. Williams
Review Article

Abstract

Allopurinol is the drug most widely used to lower the blood concentrations of urate and, therefore, to decrease the number of repeated attacks of gout. Allopurinol is rapidly and extensively metabolised to oxypurinol (oxipurinol), and the hypouricaemic efficacy of allopurinol is due very largely to this metabolite.

The pharmacokinetic parameters of allopurinol after oral dosage include oral bioavailability of 79 ± 20% (mean ± SD), an elimination half-life (t1/2) of 1.2 ± 0.3 hours, apparent oral clearance (CL/F) of 15.8 ± 5.2 mL/min/kg and an apparent volume of distribution after oral administration (Vd/F) of 1.31 ± 0.41 L/kg. Assuming that 90mg of oxypurinol is formed from every 100mg of allopurinol, the pharmacokinetic parameters of oxypurinol in subjects with normal renal function are a t1/2 of 23.3 ± 6.0 hours, CL/F of 0.31 ± 0.07 mL/min/kg, Vd/F of 0.59 ± 0.16 L/kg, and renal clearance (CLR) relative to creatinine clearance of 0.19 ±0.06. Oxypurinol is cleared almost entirely by urinary excretion and, for many years, it has been recommended that the dosage of allopurinol should be reduced in renal impairment. A reduced initial target dosage in renal impairment is still reasonable, but recent data on the toxicity of allopurinol indicate that the dosage may be increased above the present guidelines if the reduction in plasma urate concentrations is inadequate. Measurement of plasma concentrations of oxypurinol in selected patients, particularly those with renal impairment, may help to decrease the risk of toxicity and improve the hypouricaemic response. Monitoring of plasma concentrations of oxypurinol should also help to identify patients with poor adherence. Uricosuric drugs, such as probenecid, have potentially opposing effects on the hypouricaemic efficacy of allopurinol. Their uricosuric effect lowers the plasma concentrations of urate; however, they increase the CLR of oxypurinol, thus potentially decreasing the influence of allopurinol. The net effect is an increased degree of hypouricaemia, but the interaction is probably limited to patients with normal renal function or only moderate impairment.

Keywords

Gout Losartan Allopurinol Fenofibrate Probenecid 
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.

Notes

Acknowledgements

The authors gratefully acknowledge the help of Dr Pal Pacher and Associate Prof. J.B. Ziegler for help with references on allopurinol and Prof. K. Turnheim for the supply of his experimental data. No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Richard O. Day
    • 1
  • Garry G. Graham
    • 1
  • Mark Hicks
    • 1
  • Andrew J. McLachlan
    • 2
  • Sophie L. Stocker
    • 2
  • Kenneth M. Williams
    • 1
  1. 1.School of Medical Sciences, Faculty of Medicine, University of New South Wales and Department of Clinical Pharmacology and ToxicologySt Vincent’s HospitalSydneyAustralia
  2. 2.Faculty of PharmacyUniversity of Sydney and Centre for Education and Research on Aging, Concord HospitalSydneyAustralia

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