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.

pharmacology

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).

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.

half life

6-12 hours

route of elimination

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

drug interactions

Acetylsalicylic acid: Acetylsalicylic acid decreases the uricosuric effect of probenecid.

Bismuth Subsalicylate: The salicylate, bismuth subsalicylate, decreases the uricosuric effect of probenecid.

Cefaclor: Probenecid may increase the serum level of cefaclor.

Cefadroxil: Probenecid may increase the serum level of cefadroxil.

Cefamandole: Probenecid may increase the serum level of cefamandole.

Cefazolin: Probenecid may increase the serum level of cefazolin.

Cefepime: Probenecid may increase the serum level of cefepime.

Cefixime: Probenecid may increase the serum level of cefixime.

Cefmetazole: Probenecid may increase the serum level of cefmatzole.

Cefonicid: Probenecid may increase the serum level of cefonicib.

Cefotaxime: Probenecid may increase the serum level of cefotaxime.

Cefotetan: Probenecid may increase the serum level of cefotetan.

Cefoxitin: Probenecid may increase the serum level of cefoxitin.

Cefprozil: Probenecid may increase the serum level of cefprozil.

Cefradine: Probenecid may increase the serum level of cefradine.

Ceftizoxime: Probenecid may increase the serum level of ceftizoxime.

Cefuroxime: Probenecid may increase the serum level of cefuroxime.

Cephalexin: Probenecid may increase the serum level of cephalexin.

Cephaloglycin: Probenecid may increase the serum level of cephaloglycin.

Cephalothin Group: Probenecid may increase the serum level of cephalothin.

Diflunisal: Probenecid increases toxicity of diflunisal

Ganciclovir: Probenecid increases the effect and toxicity of ganciclovir/valganciclovir

Indomethacin: Probenecid increases the effect/toxicity of indomethacin

Ketorolac: Probenecid increases toxicity of ketorolac

Loracarbef: Probenecid may increase the serum level of loracarbef.

Magnesium salicylate: The salicylate, magnesium salicylate, decreases the uricosuric effect of probenecid.

Methotrexate: Probenecid increases the effect and toxicity of methotrexate

Moxalactam Derivative: Probenecid may increase the serum level of the moxalactam derivative.

Salicylate-sodium: The salicylate, salicylate-sodium, decreases the uricosuric effect of probenecid.

Salsalate: The salicylate, salsalate, decreases the uricosuric effect of probenecid.

Trisalicylate-choline: The salicylate, trisalicylate-choline, decreases the uricosuric effect of probenecid.

Valganciclovir: Probenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir.

Zidovudine: Rash, malaise, myalgia