Probenecid

Probenecid

200px
Systematic (IUPAC) name
4-(dipropylsulfamoyl)benzoic acid
Clinical data
Trade names	Probalan
AHFS/Drugs.com	monograph
MedlinePlus	a682395
Routes of administration	oral
Pharmacokinetic data
Protein binding	75-95%
Biological half-life	2-6 hours (dose: 0.5-1 g)
Excretion	renal (77-88%)
Identifiers
CAS Number	57-66-9 Y
ATC code	M04AB01 (WHO)
PubChem	CID: 4911
IUPHAR/BPS	4357
DrugBank	DB01032 Y
ChemSpider	4742 Y
UNII	PO572Z7917 Y
KEGG	D00475 Y
ChEMBL	CHEMBL897 Y
Chemical data
Formula	C13H19NO4S
Molecular mass	285.36 g/mol
SMILES O=S(=O)(N(CCC)CCC)c1ccc(C(=O)O)cc1
InChI InChI=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) Y Key:DBABZHXKTCFAPX-UHFFFAOYSA-N Y
(verify)

Probenecid, also sold under the brandname Probalan, is a medication 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 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. 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.

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.

Pharmacology

Probenecid probably has several pharmacological targets, including blocking pannexins. Probenecid is also useful in the treatment of gout where the mechanism of action is believed to be focused on the kidney. Probenecid interferes with the kidneys' organic anion transporter (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 reabsorption 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).

Pharmacokinetics

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

History

During World War II, probenecid was used to extend limited supplies of penicillin.

See also

• Probenecid and colchicine