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Lack of effect of hydrochlorothiazide and low-dose aspirin on the renal clearance of urate and oxypurinol after a single dose of allopurinol in normal volunteers

  • Pharmacokinetics and Disposition
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Abstract

Aims

To determine whether low-dose aspirin and hydrochlorothiazide (HCTZ) affect the renal clearance of oxypurinol and/or urate.

Methods

Healthy volunteers (n = 8) were treated with allopurinol (600 mg, control), and allopurinol (600 mg) co-administered with single doses of aspirin (100 mg) or HCTZ (25 mg) or a combination of the two.

Results

Hydrochlorothiazide, low-dose aspirin or a combination of the two, when co-administered with allopurinol, did not significantly alter (P > 0.05) the renal clearance of oxypurinol or urate. In particular, aspirin and HCTZ, when taken together and with allopurinol, did not change (P > 0.05) oxypurinol fractional renal clearance (allopurinol alone: 0.217, 0.173–0.262; combined: 0.202, 0.155–0.250) or urate fractional renal clearance (allopurinol alone: 0.066, 0.032–0.099; combined: 0.058, 0.038–0.078).

Conclusions

A single, low-dose of aspirin or an anti-hypertensive dose of hydrochlorothiazide, when administered alone or together with allopurinol, are unlikely to alter the hypouricaemic effect of allopurinol. The effect of chronic aspirin and HCTZ dosing taken together upon the efficacy of chronic allopurinol therapy in patients with hyperuricaemia needs to be investigated.

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Acknowledgements

The research was supported by an Arthritis Australia National Research Grant and an NH&MRC Program Grant 568612.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital, Xavier Level 2, Darlinghurst, NSW, 2010, Australia

    Daniel Y. Ng, Garry G. Graham, Kenneth M. Williams & Richard O. Day

  2. Department of Pharmacology, School of Medical Sciences, University of New South Wales, Darlinghurst, NSW, Australia

    Daniel Y. Ng, Garry G. Graham, Kenneth M. Williams & Richard O. Day

  3. Faculty of Pharmacy, University of Sydney, Sydney, Australia

    Sophie L. Stocker

Authors
  1. Daniel Y. Ng
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  2. Sophie L. Stocker
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  3. Garry G. Graham
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  4. Kenneth M. Williams
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  5. Richard O. Day
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Correspondence to Richard O. Day.

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Ng, D.Y., Stocker, S.L., Graham, G.G. et al. Lack of effect of hydrochlorothiazide and low-dose aspirin on the renal clearance of urate and oxypurinol after a single dose of allopurinol in normal volunteers. Eur J Clin Pharmacol 67, 709–713 (2011). https://doi.org/10.1007/s00228-010-0963-6

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  • DOI: https://doi.org/10.1007/s00228-010-0963-6

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