Probenecid

Probenecid (Benuryl) is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.

Probenecid competitively inhibits the renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

It was developed as an alternative to caronamide.

Uses
In one study, probenecid was shown to more than double blood concentrations of oseltamivir (trade name Tamiflu), an antiviral drug used to combat influenza. This is significant because nations are currently stockpiling oseltamivir in anticipation of an influenza pandemic, and there could be supply shortages. During World War II, probenecid was used to extend limited supplies of penicillin, and is still currently used to increase antibiotic concentrations in serious infections.

It has also found use as a masking agent.

Mechanism
In the kidneys probenecid is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule.

Probenecid's exact mechanism is explained as follows. The kidney's organic anion transporter (OAT) reclaims uric acid from the urine and returns it to the plasma. Probenecid interferes with these systems. If probenecid (an organic acid) is administered to a patient, the OAT binds to probenecid instead of to uric acid, preventing the reabsorption of uric acid. As a result, more uric acid leaves the body in the urine, lowering the uric acid concentration in the plasma. This is an example of the way in which competition between substrates transported across cell membranes has been put to use in medicine.