OBJECTIVE: To investigate whether fenofibrate increases the clearance of purine bases (hypoxanthine, xanthine, uric acid) and oxypurinol. METHODS: We administered fenofibrate (150 mg) 3 times a day for 3 days, and then allopurinol (300 mg) 4 h after the last administration of fenofibrate, to 5 healthy subjects. Ten hours later, a clearance study was done. RESULTS: Following 3 day administration of fenofibrate, fractional clearance of xanthine, uric acid, and oxypurinol increased by 41% (p < 0.05), 101% (p < 0.01), and 51% (p < 0.01), respectively, compared to baseline values, while the respective plasma concentrations decreased by 46% (p < 0.05), 46% (p < 0.05), and 19% (p < 0.05). CONCLUSION: Our results suggest that fenofibrate, fenofibric acid, or fenofibrate derivatives can increase fractional clearance of xanthine, uric acid, and oxypurinol by acting on their common renal pathways. It is suggested that the hypouricemic effect of combination therapy using allopurinol and fenofibrate may be less than additive.
OBJECTIVE: To investigate whether fenofibrate increases the clearance of purine bases (hypoxanthine, xanthine, uric acid) and oxypurinol. METHODS: We administered fenofibrate (150 mg) 3 times a day for 3 days, and then allopurinol (300 mg) 4 h after the last administration of fenofibrate, to 5 healthy subjects. Ten hours later, a clearance study was done. RESULTS: Following 3 day administration of fenofibrate, fractional clearance of xanthine, uric acid, and oxypurinol increased by 41% (p < 0.05), 101% (p < 0.01), and 51% (p < 0.01), respectively, compared to baseline values, while the respective plasma concentrations decreased by 46% (p < 0.05), 46% (p < 0.05), and 19% (p < 0.05). CONCLUSION: Our results suggest that fenofibrate, fenofibric acid, or fenofibrate derivatives can increase fractional clearance of xanthine, uric acid, and oxypurinol by acting on their common renal pathways. It is suggested that the hypouricemic effect of combination therapy using allopurinol and fenofibrate may be less than additive.
Authors: Richard O Day; Garry G Graham; Mark Hicks; Andrew J McLachlan; Sophie L Stocker; Kenneth M Williams Journal: Clin Pharmacokinet Date: 2007 Impact factor: 6.447