Probenecid
4-(dipropylsulfamoyl)benzoic acid
Also known as: Benemid · Benuryl · probenecidas · probenecidum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Reptiles
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Gout | 250 mg PO q12h; can be increased as needed. | PO | q12h | — | 🌎 NA |
| Gout | 40 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Gout | 250 mg (total dose) PO twice daily; may increase as needed. | PO | twice daily | — | 🌎 NA |
- Gout: Suggested dosage based upon human data as dose is not established for reptiles.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Probenecid is a sulfonamide derivative primarily utilized as a uricosuric agent and a renal tubular secretion inhibitor.
- Veterinary Use: While clinical use in small mammals is limited, it is particularly valuable in reptilian medicine for the management of gout (hyperuricemia).
- Pharmacological Utility: Historically and pharmacologically, probenecid is famous for its ability to inhibit the renal excretion of weak organic acids, notably beta-lactam antibiotics (penicillins and cephalosporins). By doing so, it significantly prolongs their half-life and elevates serum concentrations.
- Clinical Pearl: In dogs, probenecid has an exceptionally long elimination half-life (~18 hours) compared to humans (6.5 hours), making it theoretically advantageous for extending the dosing intervals of expensive or rapidly cleared medications, though robust clinical trials in dogs remain sparse.
Mechanism of action
Probenecid exerts its effects via competitive inhibition at the proximal renal tubules:
- Uricosuric Effect: Competitively inhibits the Urate Transporter 1 (URAT1) on the apical membrane of the proximal tubule → prevents the reabsorption of uric acid from the urine back into the blood → enhances uric acid excretion and lowers serum urate levels.
- Secretion Inhibition: Competitively inhibits Organic Anion Transporters (OAT1, OAT3) on the basolateral membrane → prevents the active tubular secretion of weak organic acids (e.g., penicillins, cephalosporins, NSAIDs) from the blood into the urine → prolongs the systemic half-life of these drugs.
Safety & warnings
Contraindications
- Patients with or susceptible to uric acid renal or bladder calculus formation
- Urate nephropathy (e.g., cancer chemotherapy with rapidly cytolytic agents)
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Gout in birds (can exacerbate the condition)
Adverse effects
- Headache (humans)
- Inappetence
- Nausea
- Mild vomiting
- Rashes
- Increased rate of gouty attacks initially (if no prophylaxis)
- Hypersensitivity (rare)
- Bone marrow suppression (rare)
- Hepatotoxicity (rare)
- Nephrotic syndrome (rare)
Precautions
Renal Function: Probenecid requires sufficient renal function to be effective; efficacy decreases with increasing renal function impairment. Avian Patients: Not usually recommended for treating gout in birds as it can exacerbate the condition. Laboratory Alterations: May cause false-positive urine glucose (cupric sulfate method), falsely elevated theophylline levels, decreased 17-ketosteroid urine concentrations, and altered renal clearance study results.
Drug interactions
Increased acyclovir serum concentrations; probenecid can decrease renal excretion
Increased chance of uric acid nephropathy
Salicylates antagonize the uricosuric effects of probenecid
Probenecid may prolong action or reduce time for onset of action
Probenecid may increase serum concentrations by reducing renal excretion
Probenecid may increase serum concentrations by reducing renal excretion (does not affect clavulanic acid)
Probenecid decreases elimination; hypoglycemia is possible
Probenecid reduces renal tubular secretion of ciprofloxacin by about 50%. Significantly reduces renal excretion of enrofloxacin in goats.
Possible accumulation of dapsone or its active metabolites
Increased serum furosemide levels
Probenecid may increase and prolong heparin's effects
Probenecid may increase levels; increased risks for toxicity
Probenecid may increase plasma levels and increase risks for toxicity
Reduced urine levels; increased chance for systemic toxicity
Probenecid may increase serum concentrations by reducing renal excretion
Probenecid may reduce hepatic uptake of rifampin and serum levels can be increased; use together is not recommended
Decreases renal elimination of sulfonamides, may increase risks for sulfonamide toxicity without therapeutic benefit
Anesthesia may be extended or dose required for anesthesia decreased
Monitoring
- Serum uric acid
- Urine uric acid
- Acid-base balance (if concomitant urine alkalinization is used)
Pharmacokinetics
Half-life
Absorption
Dogs: Oral bioavailability information not located. Mares: Oral bioavailability approximately 90%. Humans: Rapid and complete absorption after oral administration.
Distribution
Dogs: Apparent volume of distribution at steady state is 0.46 L/kg. Exhibits biphasic concentration-dependent plasma protein binding (binds less to plasma proteins than in humans). Mares: Highly bound (99.9%) to equine plasma proteins.
Metabolism
Humans: Converted in the liver to glucuronidated, carboxylated, and hydroxylated compounds that have uricosuric and renal tubular secretion inhibition activity.
Elimination
Dogs: Plasma clearance is 0.343 mL/min/kg. Humans: Elimination half-life is dosage dependent (larger dosages have longer half-lives).
Overdose
Limited information is available in veterinary species.
- Human Data: One massive (>45 g) overdose caused CNS stimulation, seizures, protracted vomiting, and respiratory failure.
- Management: Handle initially using standardized protocols for removal of drug from the gut and preventing absorption. Treat supportively. Use caution co-administrating drugs that may compete with probenecid for tubular secretion. Consider contacting an animal poison control center for guidance.
Available products
Formulations
- Tablets
Human-labeled
- Probenecid Tablets: 500 mg
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Probenecid tablets should be stored at room temperature in well-closed containers. Expiration dates are generally 3-5 years after manufacture.
Client information
Important Note: Probenecid is rarely used in dogs and cats, and its safety profile in these species is not fully established. It is more commonly prescribed for exotic pets, particularly reptiles.
- Purpose: Used to treat gout in reptiles or to intentionally prolong the effects of certain antibiotics in the body.
- Administration: Give exactly as directed by your veterinarian. Do not give any new medications or supplements without consulting your vet, as probenecid interacts with many common drugs.
- Side Effects: Watch for signs of stomach upset (loss of appetite, nausea, vomiting). Contact your vet if you notice any unusual behavior or symptoms.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.