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Channelistas (talk | contribs) →Pharmacology: pretty major action of probenecid is block of pannexins. I've added that and retained the existing material. |
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==Pharmacology== |
==Pharmacology== |
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Probenecid |
Probenecid probably has several pharmacological targets, including blocking [[pannexin]]s.<ref name="pmid18596212">{{cite journal | author = Silverman W, Locovei S, Dahl G | title = Probenecid, a gout remedy, inhibits pannexin 1 channels | journal = Am. J. Physiol., Cell Physiol. | volume = 295 | issue = 3 | pages = C761–7 |date=September 2008 | pmid = 18596212 | doi = 10.1152/ajpcell.00227.2008 | pmc = 2544448 }}</ref> |
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Probenecid is also useful in the treatment of goat where the mechanism of action is believed to be focussed on the kidney. Probenecid interferes with the kidneys' [[Organic anion-transporting polypeptide|organic anion transporter]] (OAT), which reclaims uric acid from the urine and returns it to the plasma.<ref name="pmid2962517">{{cite journal |author=Hsyu PH, Gisclon LG, Hui AC, Giacomini KM |title=Interactions of organic anions with the organic cation transporter in renal BBMV |journal=Am. J. Physiol. |volume=254 |issue=1 Pt 2 |pages=F56–61 |date=January 1988 |pmid=2962517 |doi= |url=http://ajprenal.physiology.org/cgi/pmidlookup?view=reprint&pmid=2962517}}</ref> 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). |
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==Pharmacokinetics== |
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==See also== |
==See also== |
Revision as of 11:53, 22 September 2014
Clinical data | |
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Trade names | Probalan |
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 | |
IUPHAR/BPS | |
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 (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
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
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.[5] Probenecid is also useful in the treatment of goat where the mechanism of action is believed to be focussed 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
In the kidneys, probenecid is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule.
See also
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.
- ^ 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}}
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ignored (help) - ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)