Probenecid
Probenecid is a renal organic-anion transport inhibitor with limited veterinary clinical use. Historical applications include alteration of beta-lactam elimination and empirical treatment of reptile gout. Research has also examined inhibition of tartaric-acid uptake in canine kidney cells. That cellular finding is distinct from demonstration of treatment efficacy after grape or raisin ingestion.
Group
Organic anion transport inhibitor
Mechanism of Action
Probenecid inhibits renal organic-anion transport pathways, including OAT1-mediated transport. Reduced tubular secretion can prolong exposure to selected organic-acid drugs, while inhibition of cellular uptake can reduce entry of certain transported compounds into proximal tubular cells. Its uricosuric action in humans involves reduced urate reabsorption; species differences in renal urate handling limit direct extrapolation of that effect.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Investigational single-dose exposure | Reference only | PO | Once | Healthy-dog pharmacokinetic study: 50 mg/kg once orally. This study exposure does not establish a treatment dose for grape or raisin ingestion, or a repeat-dosing regimen. |
Reptiles
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Gout | 40 mg/kg | PO | Every 12 h | Empirical reptile regimen; requires adequate renal function and hydration and assessment of urate-stone risk. |
| Human-derived fixed gout regimen | Reference only | PO | Every 12 h | A 250 mg total amount twice daily, increased as needed, was extrapolated from human data; no reptile size definition or established species dose accompanies it. Do not apply as a universal fixed amount. |
Indications
- Adjunctive prolongation of beta-lactam exposure during treatment of selected susceptible bacterial infections within a defined antimicrobial protocol.
- Historical empirical treatment of reptile gout or hyperuricemia, with uncertain efficacy and an unestablished species-specific uricosuric response.
Contraindications
- Hypersensitivity
- Uric acid urolithiasis or predisposition to urate calculi
- Urate nephropathy
- Avian gout for which probenecid may worsen disease
Interactions
- Can increase exposure to drugs eliminated through renal organic-anion transport, including several beta-lactams and methotrexate.
- Salicylates antagonize the uricosuric effect.
- Can raise acyclovir, selected beta-lactam, sulbactam/tazobactam, NSAID and oseltamivir exposure. This is not universal: ceftriaxone, ceftazidime, cefoperazone and clavulanate do not share the cited tubular-secretion interaction.
- Nitrofurantoin urine concentrations may fall while systemic toxicity risk rises.
- Can prolong heparin, certain benzodiazepine or thiopental effects and increase sulfonylurea hypoglycemia risk.
- Rifampin interaction is unpredictable and may increase toxicity.
Adverse effects
- Veterinary adverse-event frequency is not established
- Potential gastrointestinal intolerance
Toxicity
No validated animal overdose threshold is established; monitor renal function and interacting drug exposure.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Probenecid tablets 500 mg Single-active probenecid; avoid substitution of fixed colchicine combinations. | Tablet | 500 mg / tablet | PO |
Monitoring and Administration
A six-dog PK study used one 50 mg/kg oral dose and found good absorption without clinically relevant adverse effects in those healthy dogs.
That exposure did not establish efficacy for grape/raisin poisoning or safety in dogs with renal injury. Do not replace established poisoning management with an experimental transporter inhibitor.
Assess renal function, serum/urine uric acid and hydration; impaired renal function reduces uricosuric effectiveness. If urine alkalinization is used, follow acid-base status.
Probenecid may produce false-positive copper-reduction urine glucose results and alter renal clearance tests based on transported tracers. Store tablets tightly closed at room temperature.