Background Fenofibrate is an established treatment for various forms of hyperlipidaemia and is unique amongst the fibric acid derivatives due to its ability to lower serum urate. This urate-lowering effect has not, however, been assessed in patients established on allopurinol, the most widely used drug in the prevention of gout.
Objectives To assess the short-term urate lowering effect of fenofibrate in patients with hyperuricaemia and gout already treated with allopurinol.
Methods 11 patients (10M:1F), mean age 56.5 (range 38–74) with a history of either chronic tophaceous or interval gout in association with hyperuricaemia were assessed in an open crossover study. Each had been treated with allopurinol 300 mg/day or more for at least 3 months and had been free of acute gout for a minimum of 1 month. Each patient received micronised fenofibrate 200 mg once daily for 3 weeks. Before this was commenced, the following were measured: serum urate and creatinine, 24 hr urinary output of urate and creatinine, liver function tests, creatine kinase and fasting serum lipids These were repeated at the end of fenofibrate therapy and again 3 weeks later. Allopurinol was continued throughout the study period.
Results Fenofibrate was associated with a 24% reduction in serum urate after 3 weeks of treatment (mean 0.36 ± 0.11 vs 0.29 ± 0.07 mmol/l; p = 0.002). The urate-lowering effect was rapidly reversed on its withdrawal (0.29 ± 0.07 vs 0.37 ± 0.09 mmol/l). There was a rise in urate clearance of 56% (6.7 ± 3.1 vs 10.5 ± 5.6 ml/min NR 6–11; p = 0.005) without any significant change in creatinine clearance. The largest reductions in serum urate occurred in patients with the highest levels at baseline. Both total cholesterol and triglyceride levels in the serum fell, but this was not statistically significant in either case (5.9 ± 1.0 vs 5.3 ± 0.9 mmol/l; p = 0.16 and 2.34 ± 1.11 vs 1.77 ± 0.66 mmol/l; p = 0.15 respectively). Alkaline phosphatase activity was reduced in each patient, confirming compliance with fenofibrate (70 ± 15 vs 53 ± 12U/l). Importantly, none of the group developed acute arthritis whilst taking fenofibrate, and the three who continue to take the drug remain free of gouty attacks.
Conclusion Fenofibrate rapidly lowers serum urate by a significant degree in patients with hyperuricaemia who are already established on allopurinol prophylaxis. No adverse effects were seen, in particular a flare of gout. Fenofibrate is a potential novel treatment for hyperuricaemia and the prevention of gout. In particular it may have a useful dual role in patients with coexisting hyperuricaemia and hyperlipidaemia.
Bastow MD, et al. Hypertriglyceridaemia & hyperuricaemia: effects of two fibric acid derivatives (bezafibrate & fenofibrate) in a double-blind, placebo-controlled trial. Metabolism 1988;37:217–20
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