Probenecid: Effects, Uses & Risks

Probenecid is a second-line drug for hyperuricemia and gout. It inhibits the URAT1 exchanger in the kidney, increasing the release of urea into the urine while decreasing the excretion of organic anions. Probenecid interacts with numerous other drugs.

What is probenecid?

Because the drug stimulates the body to excrete uric acid, probenecid belongs to the group of uricosuric drugs. Its field of application is the treatment of hyperuricemia and gout, the latter being a consequence of hyperuricemia. Probenecid is a second-line agent: it is not the best option for first-line treatment in many cases. The active ingredient, with the molecular formula C13H19NO4S, is a solid and has a slightly bitter taste. As a drug, the crystals are often in tablet form. MSD Sharp und Dohme GmbH patented the preparation under the name Santuril. It was originally intended to ensure the supply of penicillin during World War II, because probenecid can increase the effect of penicillin, so a lower dose is required when the two drugs are combined. In practice, however, the drug was not used because probenecid development was not completed until 1952.

Pharmacologic action

In the human body, the kidney produces urine, first forming primary urine. From this, the organ recovers various substances, including electrolytes and urea. In this filtration process, urea serves to shift the osmotic gradient that allows fluid and substances dissolved in it to diffuse across the membrane. Upon reabsorption, the URAT1 exchanger – comparable to a revolving door – takes up organic anions on one side and retrieves urea on the other. Probenecid intervenes in this process: The reabsorption of uric acid decreases because the drug interferes with the exchanger. As a result, the human body releases more uric acid through the urine than usual. This process lowers the level of uric acid in the blood, which is responsible for hyperuricemia and joint problems caused by it. In return, when probenecid reduces the activity of the URAT1 exchanger, more organic anions remain in the body. In this way, probenecid may also affect the action of other drugs if the body also excretes these molecules in lower amounts.

Medical application and use

The drug is indicated for the treatment of hyperuricemia or the gout that results from it, but it is not the first-line treatment option. Instead, probenecid is usually used only after efforts with other agents have been unsuccessful. It is also approved for this purpose in Germany. Medicine defines hyperuricemia as a pathologically elevated uric acid level that exceeds 6.7 mg/dl (women) or 7.4 ml/dl (men) in blood serum. Symptoms do not manifest in hyperuricemia in every case. However, if the uric acid crystallizes as a salt in the joints, gout develops. In the course of an acute attack, inflammatory symptoms appear at the affected joint. They are often accompanied by pain. During an acute attack of gout, probenecid is contraindicated. In response to the deposited uric acid salts in the joints, the cartilage hardens and thickens. This stage is also known as chronic gout. Although most people are 30-40 years old at onset, in rare cases gout can occur in childhood. However, probenecid is not suitable for children younger than 2 years.

Risks and side effects

Probenecid is not suitable for treatment in patients with renal impairment. This is also true if there is an increased likelihood of developing kidney stones. In addition, the drug is contraindicated in hypersensitivity and presence of an acute gout attack. Potential side effects of probenecid include various skin reactions such as itching, hair loss, and gingivitis, as well as digestive problems such as bloating and nausea. In addition, headache, drowsiness, and loss of appetite may occur. Interactions are possible between probenecid and many other medications. In most cases, probenecid increases the concentration of the other active ingredients in the blood serum and can thus alter their effect.Other agents, for example, acetylsalicylic acid (ASA), may reduce the therapeutic effect of probenecid or, in other cases, lead to increased risks of effect.