Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Relationship Between Serum Urate and Plasma OxypurinolIs There a Target Plasma Oxypurinol Concentration to Achieve Serum Urate 6mg/Dl
Stamp1, Lisa, O'Donnell2, J.L., Zhang3, M., Frampton4, C., Chapman3, PT, Barclay3, M.
Allopurinol is the most commonly used urate lowering therapy. The most feared adverse effect of allopurinol is the allopurinol hypersensitivity syndrome (AHS) which can be fatal. It has been suggested that impaired renal function, concomitant diuretic therapy and plasma oxypurinol >100mmol/L are associated with AHS. A therapeutic range of plasma oxypurinol 30100mmol/L 69 hours post dose has been suggested. We wished to determine the relationship between plasma oxypurinol and serum urate (SUA) and the accuracy of the postulated therapeutic oxypurinol range.
Patients with gout on stable dose allopurinol for at least one month were recruited. Allopurinol dose was gradually increased to obtain the target SUA <=6mg/dL. Patients were seen monthly until SUA was <=6mg/dL for 3 consecutive months. Then patients were seen 3 monthly until at least 12 months after study entry. Plasma oxypurinol at 69 hours post dose was determined at each visit using HPLC.
45 patients were enrolled, mean age 59.3 years (2783), 93.3% male. Mean CrCl was 61.9ml/min (19132) and mean SUA 7.4 mg/dL (610.8mg/dL). The mean allopurinol dose at baseline was 221.1mg/d (100400mg/d) and mean plasma oxypurinol 92.3mmol/L (42.5266.7mmol/L). 31/36 (85%) patients achieved the target SUA <6mg/dL at the 12month endpoint, mean SUA 5mg/dL (3.95.9mg/dL), mean plasma oxypurinol 141.8mmol/L (71.6 359.8mmol/L) and mean allopurinol dose 359.7 mg/d (150600mg/d). Using mixed-effect linear modelling, allowing for individual patient effects, there was a significant relationship between allopurinol dose and plasma oxypurinol concentration (p<0.001). An increase of allopurinol dose by 100mg resulted in a mean increase in plasma oxypurinol of 46.8mmol/L. Additionally, mixed-effect linear modelling allowing for individual patient effects revealed a significant inverse relationship between SUA and plasma oxypurinol (p<0.001). A mean increase in plasma oxypurinol of 47mmol/L resulted in a 0.1mmol/L reduction in SUA. For those patients who achieved a SUA <6mg/dL, plasma oxypurinol was on average 136.8mmol/L at the first point when SUA reached the target. In comparison, plasma oxypurinol was on average 100.8mmol/L when SUA was >6mg/dL. There were no serious adverse events despite the higher plasma oxypurinol concentrations.
Increasing allopurinol dose results in an increase in plasma oxypurinol and a reduction in SUA. In general plasma oxypurinol, concentrations above the proposed therapeutic range were required to achieve SUA <6mg/dL. Larger studies will be required to determine the role of dose adjustment based on plasma oxypurinol concentrations.
To cite this abstract, please use the following information:
Stamp, Lisa, O'Donnell, J.L., Zhang, M., Frampton, C., Chapman, PT, Barclay, M.; Relationship Between Serum Urate and Plasma OxypurinolIs There a Target Plasma Oxypurinol Concentration to Achieve Serum Urate 6mg/Dl [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1502