Probenecid
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| Clinical data | |
|---|---|
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682395 |
| Routes of administration | oral |
| ATC code | |
| Pharmacokinetic data | |
| Protein binding | 75-95% |
| Elimination half-life | 2-6 hours (dose: 0.5-1 g) |
| Excretion | renal (77-88%) |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.000.313 |
| Chemical and physical data | |
| Formula | C13H19NO4S |
| Molar mass | 285.36 g/mol g·mol−1 |
| 3D model (JSmol) | |
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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.
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]
Drug Interactions
Some of the important clinical interactions of Probenecid include those with Captopril, Indomethacin, Ketoprofen, Ketorolac, Naproxen, Cephalosporins, Quinolones, Penicillins, Methotrexate, Zidovudine, Gancyclovir, Aciclovir. In all these interactions the excretion of these drugs is reduced due to Probenecid.
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 kidney's 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 re-absorption 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 gap junction (connexin) channels [6]
See also
References
- ^ MASON RM (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.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Butler D (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature. 438 (7064): 6. doi:10.1038/438006a. PMID 16267514.
- ^ 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.
{{cite journal}}: Unknown parameter|author-separator=ignored (help) - ^ Morra V, Davit P, Capra P, Vincenti M, Di Stilo A, Botrè F (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". Am. J. Physiol. 254 (1 Pt 2): F56–61. PMID 2962517.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ DOI: 10.1152/ajpcell.00227.2008