Probenecid

Probenecid

Probenecid
Systematic (IUPAC) name
4-(dipropylsulfamoyl)benzoic acid
Clinical data
Trade names Probalan
AHFS/Drugs.com
MedlinePlus
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 Registry Number  Y
ATC code M04
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEMBL  Y
Chemical data
Formula C13H19NO4S
Molecular mass 285.36 g/mol
 Y   

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[1] to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

Contents

  • Medical uses 1
  • Drug interactions 2
  • Pharmacology 3
  • Pharmacokinetics 4
  • History 5
  • See also 6
  • References 7

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.[2]

It has also found use as a masking agent.[3]

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

  1. ^ MASON RM (June 1954). "Studies on the Effect of Probenecid ('Benemid') in Gout". Ann. Rheum. Dis. 13 (2): 120–30.  
  2. ^ Cox, VC; Zed, PJ (March 2004). "Once-daily cefazolin and probenecid for skin and soft tissue infections.". The Annals of pharmacotherapy 38 (3): 458–63.  
  3. ^ 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.  
  4. ^ 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.  
  5. ^ 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.  
  6. ^ Butler D (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature 438 (7064): 6.  

References

See also

During World War II, probenecid was used to extend limited supplies of penicillin.[6]

History

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

Pharmacokinetics

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). [5]