Probenecid

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

Probenecid was developed as an alternative to caronamide.^[1] Their primary goal was to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

Uses

During World War II, probenecid was used to extend limited supplies of penicillin,^[2] and is still currently used to increase antibiotic concentrations in serious infections. In one study, probenecid was shown to more than double blood concentrations of oseltamivir (trade name Tamiflu), an antiviral drug used to combat influenza, suggesting that this property applies to antivirals as well.^[3]

It has also found use as a masking agent.^[4]

Drug Interactions

Some of the important clinical interactions of Probenecid include those with Captopril, Indomethacin, Ketoprofen, Ketorolac, Naproxen, Cephalosporins, Quinolones, Penicillins, Methotrexate, Zidovudine, Gancyclovir, Aciclovir. In all these interactions the excretion of these drugs is reduced due to Probenecid.

Pharmacology

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

Probenecid works by interfering with the kidney's organic anion transporter (OAT), which reclaims uric acid from the urine and returns it to the plasma.^[5] If probenecid (an organic acid) is present, the OAT binds preferentially to it (instead of to uric acid), preventing re-absorption of the uric acid. Hence, the urine retains more uric acid, lowering uric acid concentration in the plasma. (This is a good example of a medical usage for competition between substrates transported across cell membranes). Probenecid also inhibits pannexin channels.^[6]

See also

• Probenecid and colchicine

References