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Research ArticleArticle

Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout

Sophie L. Stocker, Garry G. Graham, Andrew J. McLachlan, Kenneth M. Williams and Richard O. Day
The Journal of Rheumatology February 2011, jrheum.101160; DOI: https://doi.org/10.3899/jrheum.101160
Sophie L. Stocker
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Garry G. Graham
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Andrew J. McLachlan
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Kenneth M. Williams
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Richard O. Day
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Abstract

Objective To investigate the pharmacokinetic and pharmacodynamic interaction between probenecid and oxypurinol (the active metabolite of allopurinol) in patients with gout.

Methods This was an open-label observational clinical study. Blood and urine samples were collected to measure oxypurinol and urate concentrations. We examined the effects of adding probenecid to allopurinol therapy upon plasma concentrations and renal clearances of urate and oxypurinol.

Results Twenty patients taking allopurinol 100–400 mg daily completed the study. Maximum coadministered doses of probenecid were 250 mg/day (n = 1), 500 mg/day (n = 19), 1000 mg/day (n = 7), 1500 mg/day (n = 3), and 2000 mg/day (n = 1). All doses except the 250 mg daily dose were divided and dosing was twice daily. Estimated creatinine clearances ranged from 28 to 113 ml/min. Addition of probenecid 500 mg/day to allopurinol therapy decreased plasma urate concentrations by 25%, from mean 0.37 mmol/l (95% CI 0.33–0.41) to mean 0.28 mmol/l (95% CI 0.24–0.32) (p < 0.001); and increased renal urate clearance by 62%, from mean 6.0 ml/min (95% CI 4.5–7.5) to mean 9.6 ml/min (95% CI 6.9–12.3) (p < 0.001). Average steady-state plasma oxypurinol concentrations decreased by 26%, from mean 11.1 mg/l (95% CI 5.0–17.3) to mean 8.2 mg/l (95% CI 4.0–12.4) (p < 0.001); and renal oxypurinol clearance increased by 24%, from mean 12.7 ml/min (95% CI 9.6–15.8) to mean 16.1 ml/min (95% CI 12.0–20.2) (p < 0.05). The additional hypouricemic effect of probenecid 500 mg/day appeared to be lower in patients with renal impairment.

Conclusion Coadministration of allopurinol with probenecid had a significantly greater hypouricemic effect than allopurinol alone despite an associated reduction of plasma oxypurinol concentrations. Australian Clinical Trials Registry ACTRN012606000276550.

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The Journal of Rheumatology
Vol. 50, Issue 2
1 Feb 2023
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Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout
Sophie L. Stocker, Garry G. Graham, Andrew J. McLachlan, Kenneth M. Williams, Richard O. Day
The Journal of Rheumatology Feb 2011, jrheum.101160; DOI: 10.3899/jrheum.101160

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Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout
Sophie L. Stocker, Garry G. Graham, Andrew J. McLachlan, Kenneth M. Williams, Richard O. Day
The Journal of Rheumatology Feb 2011, jrheum.101160; DOI: 10.3899/jrheum.101160
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