Probenecid

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Probenecid
Probenecid.svg
Probenecid ball-and-stick.png
Systematic (IUPAC) name
4-(dipropylsulfamoyl)benzoic acid
Clinical data
Trade names Probalan
AHFS/Drugs.com monograph
MedlinePlus a682395
Legal status
?
Routes oral
Pharmacokinetic data
Protein binding 75-95%
Half-life 2-6 hours (dose: 0.5-1 g)
Excretion renal (77-88%)
Identifiers
CAS number 57-66-9 YesY
ATC code M04AB01
PubChem CID 4911
IUPHAR ligand 4357
DrugBank DB01032
ChemSpider 4742 YesY
UNII PO572Z7917 YesY
KEGG D00475 YesY
ChEMBL CHEMBL897 YesY
Chemical data
Formula C13H19NO4S 
Mol. mass 285.36 g/mol
 YesY (what is this?)  (verify)

Probenecid (Lannett's 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] to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

Uses[edit]

Probenecid is primarily used to treat gout and hyperuricemia.

During World War II, probenecid was used to extend limited supplies of penicillin,[2] and is still 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 the flu, suggesting this property applies to antivirals, as well.[3]

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

Drug interactions[edit]

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[edit]

Probenecid probably has several pharmacological targets, including blocking pannexins.[5] 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.[6] 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[edit]

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

See also[edit]

References[edit]

  1. ^ MASON RM (June 1954). "Studies on the Effect of Probenecid ('Benemid') in Gout". Ann. Rheum. Dis. 13 (2): 120–30. doi:10.1136/ard.13.2.120. PMC 1030399. PMID 13171805. 
  2. ^ Butler D (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature 438 (7064): 6. doi:10.1038/438006a. PMID 16267514. 
  3. ^ Hill G, Cihlar T, Oo C et al. (2002). "The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies". Drug Metab. Dispos. 30 (1): 13–9. doi:10.1124/dmd.30.1.13. PMID 11744606. 
  4. ^ Morra V, Davit P, Capra P, Vincenti M, Di Stilo A, Botrè F (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". J Chromatogr A 1135 (2): 219–29. doi:10.1016/j.chroma.2006.09.034. PMID 17027009. 
  5. ^ Silverman W, Locovei S, Dahl G (September 2008). "Probenecid, a gout remedy, inhibits pannexin 1 channels". Am. J. Physiol., Cell Physiol. 295 (3): C761–7. doi:10.1152/ajpcell.00227.2008. PMC 2544448. PMID 18596212. 
  6. ^ Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (January 1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". Am. J. Physiol. 254 (1 Pt 2): F56–61. PMID 2962517.