Probenecid
**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.
Mecanismo: 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.
Dosificación por especie
- Gout · 250 mg PO q12h; can be increased as needed. · PO · q12h · Suggested dosage based upon human data as dose is not established for reptiles.
- Gout · 40 mg/kg PO q12h · PO · q12h
- Gout · 250 mg (total dose) PO twice daily; may increase as needed. · PO · twice daily
Las dosis son una referencia clínica para veterinarios colegiados. Confirme siempre con la ficha técnica vigente y el paciente individual.
Vías de administración
Contraindicaciones
- 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)
Efectos adversos
- 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)
Interacciones farmacológicas
- Acyclovir · Increased acyclovir serum concentrations; probenecid can decrease renal excretion
- Antineoplastics (rapidly cytolytic) · Increased chance of uric acid nephropathy
- Aspirin (and other salicylates) · Salicylates antagonize the uricosuric effects of probenecid
- Benzodiazepines (lorazepam, oxazepam) · Probenecid may prolong action or reduce time for onset of action
- Beta-lactam antibiotics · Probenecid may increase serum concentrations by reducing renal excretion
- Beta-lactamase inhibitors (sulbactam, tazobactam) · Probenecid may increase serum concentrations by reducing renal excretion (does not affect clavulanic acid)
- Chlorpropamide · Probenecid decreases elimination; hypoglycemia is possible
- Ciprofloxacin/Enrofloxacin · Probenecid reduces renal tubular secretion of ciprofloxacin by about 50%. Significantly reduces renal excretion of enrofloxacin in goats.
- Dapsone · Possible accumulation of dapsone or its active metabolites
- Furosemide · Increased serum furosemide levels
- Heparin · Probenecid may increase and prolong heparin's effects
- Methotrexate · Probenecid may increase levels; increased risks for toxicity
Monitorización
- Serum uric acid
- Urine uric acid
- Acid-base balance (if concomitant urine alkalinization is used)
Sobredosis
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.
La referencia de fármacos de VetSheet está destinada a veterinarios colegiados como apoyo a la decisión clínica, no sustituye el juicio profesional ni la ficha técnica vigente del fabricante.