Background/Purpose: Allopurinol is recommended as a first-line pharmacologic urate-lowering therapy in gout. Oxypurinol, the active metabolite of allopurinol, is entirely cleared by the kidneys. Oxypurinol clearance decreases in proportion to glomerular filtration rate (GFR) in chronic kidney disease. However, the pharmacokinetics of oxypurinol in dialysis patients is not known. We hypothesised that oxypurinol clearance in patients receiving haemodialysis will be comparable to patients with a glomerular filtration rate (GFR) of 10-20 ml/min. The purpose of this study was to describe oxypurinol pharmacokinetics in people with gout treated with hemodialysis.  

Methods: The pharmacokinetics of oxypurinol was assessed in a group of patients with gout receiving intermittent haemodialysis three times weekly for five hours per session (Hemoflow F8HPS Polysulfone dialyser). The blood flow for dialysis was 200mL/min and the dialysate flow was 500 mL/min. All subjects were taking long-term allopurinol 100 mg daily. During the study allopurinol was taken after dialysis on dialysis days. Six blood samples were collected from each subject at 0, 1, 2, 3, 4, and 5 hours after the start of dialysis for the measurement of oxypurinol plasma concentrations. Urine was collected from each subject over a 24 hour period.  A further eight blood samples were collected from each subject across a non-dialysis dosing interval at 0, 0.5, 1, 1.5, 2, 4, 6 and 24 hours after the dose. Serum urate was measured at baseline, post-dialysis (6 hours), and at the end of the study (48 hours). Oxypurinol was measured by liquid chromatography–mass spectrometry and oxypurinol clearance was calculated from the area under the concentration time curve (AUC).

Results: Six patients were recruited; five male and one female. Their median age was 63 years (28-72 years).  All had been taking allopurinol for > 1 year, were taking no other medicines for gout, and were not taking diuretics. Two patients were anuric and four had some residual renal function (urine output 0-260 ml/24 hrs). One patient was excluded after sample analysis as their results showed they were not adherent with treatment. At steady state, the oxypurinol median AUC was 30 umol/L*hr (range 23-50). The median oxypurinol clearance was 1.0 L/hr (0.60-1.3). This was higher than expected and comparable to the clearance in patients with normal kidney function. The median plasma urate concentration pre-dialysis was 5.9 mg/dL (4.7-8.9mg/dl). Serum urate dropped precipitously during dialysis and is either back to baseline (n=2) or within 80% of baseline (n=3) by 42 hours post-dialysis.

Conclusion: Allopurinol is likely to be more effective if administered after, rather than before, dialysis. Serum urate should be measured prior to dialysis to ensure target urate is maintained between dialysis. Hemodialysis was more effective at removing oxypurinol from the circulation than predicted. The dose of allopurinol in dialysis patients does not need to be restricted to 100mg daily. Further studies of allopurinol to treat gout in dialysis patients should examine conventional urate targeted dosing.