Probenecid is a uricosuric

Uricosuric

Uricosuric medications are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule...

 drug that increases uric acid

Uric acid

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...

 excretion in the urine

Urine

Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

. It is primarily used in treating gout

Gout

Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

 and hyperuricemia

Hyperuricemia

Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...

.

Probenecid was developed as an alternative to caronamide. 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

Penicillin

Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

, 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

Oseltamivir

Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...

 (trade name Tamiflu), an antiviral drug

Antiviral drug

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

 used to combat influenza

Influenza

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

, suggesting that this property applies to antivirals as well.

It has also found use as a masking agent

Masking agent

A masking agent is a reagent used in chemical analysis which reacts with chemical species that may interfere in the analysis.In sports a masking agent is used to hide or prevent detection of a banned substance or illegal drug like anabolic steroids or stimulants...

.

Drug Interactions

Some of the important clinical interactions of Probenecid include those with Captopril

Captopril

Captopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...

, Indomethacin, Ketoprofen

Ketoprofen

Ketoprofen, 2--propionic acid is one of the propionic acid class of non-steroidal anti-inflammatory drug with analgesic and antipyretic effects...

, Ketorolac

Ketorolac

Ketorolac or ketorolac tromethamine is a non-steroidal anti-inflammatory drug in the family of heterocyclic acetic acid derivative, often used as an analgesic...

, Naproxen

Naproxen

Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...

, Cephalosporins, Quinolones, Penicillins, Methotrexate

Methotrexate

Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...

, Zidovudine

Zidovudine

Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....

, Gancyclovir, Aciclovir

Aciclovir

Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...

. In all these interactions the excretion of these drugs is reduced due to Probenecid.

Pharmacology

In the kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s probenecid is filtered at the glomerulus

Glomerulus

A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...

, secreted in the proximal tubule

Proximal tubule

The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...

 and reabsorbed in the distal tubule.

Probenecid works by interfering with the kidney's organic anion transporter

Organic anion-transporting polypeptide

An organic anion-transporting polypeptide is a membrane transport protein that mediates the transport of organic anions across the cell membrane...

 (OAT), which reclaims uric acid from the urine and returns it to the plasma. 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

Pannexin

Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins...

channels.