Pharmacokinetic and pharmacodynamic interaction between XXXX and probenecid in @entity1 with @entity210 .

@entity1 @entity8 @entity6652 @entity1011 @entity210 @entity208
OBJECTIVE: To investigate the pharmacokinetic and pharmacodynamic interaction between probenecid and @entity6652 (the active metabolite of @entity208 ) in @entity1 with @entity210 . METHODS: This was an open-label observational clinical study. Blood and urine samples were collected to measure @entity6652 and urate concentrations. We examined the effects of adding probenecid to @entity208 therapy upon plasma concentrations and renal clearances of urate and @entity6652 . RESULTS: Twenty @entity1 taking @entity208 100-400 mg daily completed the study. Maximum coadministered doses of probenecid were 250 mg/day (n = 1), 500 mg/day (n = 19), 1000 mg/day (n = 7), 1500 mg/day (n = 3), and 2000 mg/day (n = 1). All doses except the 250 mg daily dose were divided and dosing was twice daily. Estimated @entity1011 clearances ranged from 28 to 113 ml/min. Addition of probenecid 500 mg/day to @entity208 therapy decreased plasma urate concentrations by 25%, from mean 0.37 mmol/l (95% CI 0.33-0.41) to mean 0.28 mmol/l (95% CI 0.24-0.32) (p < 0.001); and increased renal urate clearance by 62%, from mean 6.0 ml/min (95% CI 4.5-7.5) to mean 9.6 ml/min (95% CI 6.9-12.3) (p < 0.001). Average steady-state plasma @entity6652 concentrations decreased by 26%, from mean 11.1 mg/l (95% CI 5.0-17.3) to mean 8.2 mg/l (95% CI 4.0-12.4) (p < 0.001); and renal @entity6652 clearance increased by 24%, from mean 12.7 ml/min (95% CI 9.6-15.8) to mean 16.1 ml/min (95% CI 12.0-20.2) (p < 0.05). The additional hypouricemic effect of probenecid 500 mg/day appeared to be lower in @entity1 with @entity8 . CONCLUSION: Coadministration of @entity208 with probenecid had a significantly greater hypouricemic effect than @entity208 alone despite an associated reduction of plasma @entity6652 concentrations. Australian Clinical Trials Registry ACTRN012606000276550.
