None listed
Conditions
Brief summary
Gout is an inflammatory condition caused by the deposition of urate crystals in tissues/joints. Allopurinol is a common and effective treatment to prevent gout. Probenecid, although less common used, is also effective, but may be less effective in patients with impaired renal function. In patients with tophaceous gout or those unresponsive to allopurinol/probenecid alone, the combination is sometimes prescribed. Studies in healthy subjects have shown that although the elimination of oxypurinol (active metabolite of allopurinol) is increased when probenecid is taken concurrently with allopurinol, the combination therapy has a greater therapeutic effect (decreased plasma urate concentrations). The relevance of these findings for gouty patients is unknown. Thus, this project will examine the interaction between allopurinol and probenecid in gouty patients and determine the therapeutic effect in patients with a range of renal function.
Interventions
Patients already receiving allopurinol for at least one week will be co-administered (oral) probenecid starting at 500 mg/day. This dose will be increased (500 mg weekly to a maximum of 2g/ day) until plasma urate concentrations fall below 0.36mmol/L or are decreased by at least 20%, and no side effects have been experienced. Patients will have the following measured every 3-11 days, this being a period that approximates steady-state: plasma urate, plasma creatinine, urinary urate and urinary cr
Patients already receiving allopurinol for at least one week will be co-administered (oral) probenecid starting at 500 mg/day. This dose will be increased (500 mg weekly to a maximum of 2g/ day) until plasma urate concentrations fall below 0.36mmol/L or are decreased by at least 20%, and no side effects have been experienced. Patients will have the following measured every 3-11 days, this being a period that approximates steady-state: plasma urate, plasma creatinine, urinary urate and urinary creatinine using standard biochemical analysis and plasma and urinary oxypurinol using validated methods. During the study patients will be given prophylactic medication (e.g. NSAIDs or colchicine) to prevent acute attacks of gout in accordance with standard clinical practice.
Sponsors
Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital Sydney Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients taking allopurinol for the indication of hyperuricaemia and/or gout.
Exclusion criteria
1. A history of sensitivity to allopurinol or probenecid2. A history of nephrolithiasis3. Patients taking drugs likely to interfere with the pharmacokinetics of allopurinol or probenecid including: salicylates (high doses) 4. Drugs likely to interact with probenecid including: valaciclovir, acyclovir, famiciclovir, penciclovir, ganciclovir, zidovudine, methotrexate, lorazepam, midazolam, nitrazepam. Note: Drugs which may affect plasma urate concentrations need to be taken consistently throughout the study to avoid biasing the plasma urate concentrations.
Outcome results
None listed