Probenecid
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| Systematic (IUPAC) name | |
| 4-(dipropylsulfamoyl)benzoic acid | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682395 |
| Pregnancy cat. | ? |
| 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  |
| ATC code | M04AB01 |
| PubChem | CID 4911 |
| DrugBank | APRD00167 |
| ChemSpider | 4742 |
| UNII | PO572Z7917 |
| KEGG | D00475 |
| ChEMBL | CHEMBL897 |
| Chemical data | |
| Formula | C13H19NO4S |
| Mol. mass | 285.36 g/mol |
| SMILES | eMolecules & PubChem |
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Probenecid (Benuryl, Benemid, 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] Their primary goal was to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.
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[edit] Uses
During World War II, probenecid was used to extend limited supplies of penicillin,[2] 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 (trade name Tamiflu), an antiviral drug used to combat influenza, suggesting that this property applies to antivirals as well.[3]
It has also found use as a masking agent.[4]
[edit] Drug interactions
Some of the important clinical interactions of probenecid include those with captopril, indomethacin, ketoprofen, ketorolac, naproxen, cephalosporins, quinolones, penicillins, methotrexate, zidovudine, gancyclovir, and aciclovir. In all these interactions, the excretion of these drugs is reduced due to probenecid.
[edit] Pharmacology
In the kidneys, probenecid is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule.
Probenecid works by interfering with the kidneys' organic anion transporter (OAT), which reclaims uric acid from the urine and returns it to the plasma.[5] 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). Probenecid also inhibits pannexin channels.[6]
[edit] See also
[edit] References
- ^ 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. http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=13171805.
- ^ Butler D (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature 438 (7064): 6. doi:10.1038/438006a. PMID 16267514. http://www.nature.com/nature/journal/v438/n7064/full/438006a.html.
- ^ 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. http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11744606.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(06)01791-2.
- ^ 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. http://ajprenal.physiology.org/cgi/pmidlookup?view=reprint&pmid=2962517.
- ^ 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. http://ajpcell.physiology.org/content/295/3/C761.abstract.
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