Drug interactions with urate excretion in man

Area of Science:

• Pharmacology
• Nephrology
• Uric Acid Metabolism

Background:

• Uricosuric agents like probenecid and benzbromarone are used to lower uric acid levels.
• The interaction of antibiotics with urate transport is not fully understood.

Purpose of the Study:

• To investigate the effects of pyrazinamide and ampicillin on the uricosuric response to probenecid and benzbromarone.
• To elucidate the mechanisms of ampicillin and benzbromarone interaction with renal urate transport.

Main Methods:

• Six healthy subjects participated in the study.
• Uric acid excretion, urate clearance (Curate), and creatinine clearance (Ccreatinine) were measured over 24 hours.
• The percentage Curate/Ccreatinine was calculated for different urine collection periods.

Main Results:

• Ampicillin alone induced significant uricosuria in early (0-2 h) and late (8-24 h) periods.
• Benzbromarone significantly reduced all measured parameters of uric acid excretion.
• Ampicillin's delayed uricosuria suggests binding to proximal tubular cell receptors.

Conclusions:

• High ampicillin concentrations compete with uric acid for tubular reabsorption.
• Benzbromarone appears to utilize a pyrazinamide-sensitive urate secretion pathway, potentially causing paradoxical urate retention.
• Benzbromarone does not interfere with the probenecid-sensitive secretory transport of ampicillin.