Probenecid

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Chemical compound

title: "Probenecid" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["antigout-agents", "world-anti-doping-agency-prohibited-substances", "benzoic-acids", "cyp2c9-inhibitors", "cyp2c19-inhibitors"] description: "Chemical compound" topic_path: "general/antigout-agents" source: "https://en.wikipedia.org/wiki/Probenecid" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

::data[format=table title="Infobox drug"]

Field	Value
verifiedrevid	459812016
IUPAC_name	4-(dipropylsulfamoyl)benzoic acid
image	Probenecid.svg
image_class	skin-invert-image
width	200
image2	Probenecid ball-and-stick.png
image_class2	bg-transparent
width2	200
tradename	Probalan
Drugs.com
MedlinePlus	a682395
legal_status	Rx only
routes_of_administration	By mouth
protein_bound	75-95%
elimination_half-life	2-6 hours (dose: 0.5-1 g)
excretion	kidney (77-88%)
CAS_number_Ref
CAS_number	57-66-9
ATC_prefix	M04
ATC_suffix	AB01
PubChem	4911
IUPHAR_ligand	4357
DrugBank_Ref
DrugBank	DB01032
ChemSpiderID_Ref
ChemSpiderID	4742
UNII_Ref
UNII	PO572Z7917
KEGG_Ref
KEGG	D00475
ChEMBL_Ref
ChEMBL	897
C	13
smiles	O=S(=O)(N(CCC)CCC)c1ccc(C(=O)O)cc1
StdInChI_Ref
StdInChI	1S/C13H19NO4S/c1-3-9-14(10-4-2)19(17,18)12-7-5-11(6-8-12)13(15)16/h5-8H,3-4,9-10H2,1-2H3,(H,15,16)
StdInChIKey_Ref
StdInChIKey	DBABZHXKTCFAPX-UHFFFAOYSA-N
::

Probenecid was developed as an alternative to caronamide to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

Medical uses

Probenecid is primarily used to treat gout and hyperuricemia.

Probenecid is sometimes used to increase the concentration of some antibiotics and to protect the kidneys when given with cidofovir. Specifically, a small amount of evidence supports the use of intravenous cefazolin once rather than three times a day when it is combined with probenecid.

It has also found use as a masking agent, potentially helping athletes using performance-enhancing substances to avoid detection by drug tests.

Adverse effects

Mild symptoms such as nausea, loss of appetite, dizziness, vomiting, headache, sore gums, or frequent urination are common with this medication. Life-threatening side effects such as thrombocytopenia, hemolytic anemia, leukemia and encephalopathy are extremely rare. Theoretically probenecid can increase the risk of uric acid kidney stones.

Drug interactions

Some of the important clinical interactions of probenecid include those with captopril, indomethacin, ketoprofen, ketorolac, naproxen, cephalosporins, quinolones, penicillins, methotrexate, zidovudine, ganciclovir, lorazepam, and acyclovir. In all these interactions, the excretion of these drugs is reduced due to probenecid, which in turn can lead to increased concentrations of these.

Pharmacology

Pharmacodynamics

In gout, probenecid competitively inhibits the reabsorption of uric acid through the organic anion transporter (OAT) at the proximal tubules. This leads to preferential reabsorption of probenecid back into plasma and excretion of uric acid in urine, thus reducing blood uric acid levels and reducing its deposition in various tissues.

Probenecid also inhibits pannexin 1. Pannexin 1 is involved in the activation of inflammasomes and subsequent release of interleukin-1β causing inflammation. Inhibition of pannexin 1 thus reduces inflammation, which is the core pathology of gout.

Pharmacokinetics

In the kidneys, probenecid is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule. Probenicid lowers the concentration of certain drugs in urine drug screens by reducing renal excretion of these drugs.

Historically, probenecid has been used to increase the duration of action of drugs such as penicillin and other beta-lactam antibiotics. Penicillins are excreted in the urine at proximal and distal convoluted tubules through the same organic anion transporter (OAT) as seen in gout. Probenecid competes with penicillin for excretion at the OAT, which in turn increases the plasma concentration of penicillin.

History

During World War II, probenecid was used to extend limited supplies of penicillin. This use exploited probenecid's interference with drug elimination (via urinary excretion) in the kidneys and allowed lower doses of penicillin to be used.

Probenecid was added to the International Olympic Committee's list of banned substances in January 1988, due to its use as a masking agent.

References

(June 1954). "Studies on the effect of probenecid (benemid) in gout". Annals of the Rheumatic Diseases.
(March 2004). "Once-daily cefazolin and probenecid for skin and soft tissue infections". The Annals of Pharmacotherapy.
(December 2006). "Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis". Journal of Chromatography A.
(November 2014). "Uricosuric medications for chronic gout". The Cochrane Database of Systematic Reviews.
(March–April 1981). "Clinical pharmacokinetics of probenecid". Clinical Pharmacokinetics.
"Probenecid". U.S. National Library of Medicine.
(September 2008). "Probenecid, a gout remedy, inhibits pannexin 1 channels". American Journal of Physiology. Cell Physiology.
(January 2010). "Comprehensive Toxicology". Elsevier.
(November 2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature.
(2001). "Doping in Elite Sport: The Politics of Drugs in the Olympic Movement". Human Kinetics.

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