Probenecid Act as an Uricosuric agent: A Review

 

Mr. Mayur S. Jain1*, Dr. Shashikant D. Barhate2, Mr. Bhushan P. Gayakwad3

Shree Sureshadada Jain Institutes of Pharmaceutical Education and Research, Jammer, Maharashtra (India).

*Corresponding Author E-mail: mayurjain176@gmail.com

 

ABSTRACT

Probenecid is s prototypical uricosuric agent which is predominantly used to inhibit the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treatment of gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

 

KEYWORDS: Probenecid; Uricosuric agent; Gout

 


INTRODUCTION:

During World War II, probenecid was used to extend limited supplies of penicillin; this use exploited probenecid's interference with metabolism in the kidneys and allowed lower doses to be used. Probenecid is a uricosoric agent used in gout therapy. The combination is used in gastrointestinal tract and respiratory tract infections. The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. When Cefadroxil is co-administered with Probenecid, the renal excretion of Cefadroxil is inhibited. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubular.

 

Probenecid is very useful for the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics. A major contributing factor is its lesser efficacy among patients with diminished renal function, a common comorbidity in patients with gout.This compound belongs to the class of organic compounds known as benzene sulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring. .[1,2]

 

Structure:

 

 

Chemical formula: C13H19NO4S

Molecular weight: 285.359 g/mol

Melting point: 195°C

Water solubility: 27.1 mg/L

IUPAC Name: 4-(dipropylsulfamoyl) benzoic acid

 

PHARMACOLOGY:

Indication:

For the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics.[1,2]

 

Pharmacodynamics:

Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other β-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain β-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID).[1,3]

 

Pharmacokinetics:

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

 

Mechanism of action:

Probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Probenecid may also reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubules.[1, 2]

 

Protein binding: 75-95%

 

 

 

Route of elimination:

Excreted principally in the urine as monoacyl glucuronide and unchanged drug. Alkalinization of urine increases renal probenecid excretion.

 

Half life (t50%): 6-12 hours

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. .[1]

 

Food interactions:

1.      Increase liquid intake, avoid alcohol.

2.      Take with food to reduce irritation.

 

Medicinal uses:

1.      Probenecid is primarily used to treat gout and hyperuricemia.

2.      Probenecid is sometimes used to increase the concentration of some antibiotics and to protect the kidneys when given with cidofovir. 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.

3.      It has also found use as a masking agent, potentially helping athletes using performance-enhancing substances to avoid detection by drug tests. .[1]

 

Marketed preparations:[1,2]

Sr.No.

Name of product

Dosage form

Strength (mg)

Route

1

Benemid Tab 500mg

Tablet

500

Oral

2

Benuryl

Tablet

500

Oral

3

Probenecid

Tablet

500

Oral

4

Pro Biosan Kit

Capsule

500

Oral

5

Probenecid and Colchicine

Tablet

500 + 500

Oral

 

CONCLUSION:

The advantage of probenecid is its relatively low cost. It has a long history of use with experience worldwide in large numbers of patients. Thus probenecid is useful in many patients with gout. Also, because many of patients tend to be those with the most severe forms of gout. Probenecid is very useful for the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics.

 

ACKNOWLEDGEMENT:

The authors would like to thanks Shree. Sureshadada Jain Institutes of Pharmaceutical Education and Research, Jamner Maharashtra (India) for supporting the fulfillment of this work.

 

CONFLICT OF INTEREST:

Declared none.

 

REFERENCES:

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3.     Zed P. J. (March 2004). "Once-daily cefazolin and probenecid for skin and soft tissue infections". The journal of pharmacotherapy. 38 (3): 458–63. Doi:10.1345/aph.1d251. Pmid 14970368.

4.     Davit P. Capra P. Vincenti M, Di Stilo, Botre 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. Chromatograph. 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". American Journal of Physiology, cell physiology. 295 (3): c761–7. Doi:10.1152/ajpcell.00227.2008. Pmc 2544448. Pmid 18596212. 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.

6.     Butler D. (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature. 438 (7064): 6. Doi: 10.1038/438006a. Pmid 16267514.

 

 

 

 

 

 

 

 

Received on 20.12.2017                Modified on 19.01.2018

Accepted on 13.02.2018            © A&V Publications All right reserved

Asian J. Res. Pharm. Sci. 2018; 8(1):45-47.

DOI: 10.5958/2231-5659.2018.00010.3