probenecid
Brand: Probalan
Prototype Drug
Drug Class: uricosuric agent
Drug Family: uric acid agent
Subclass: organic anion transporter inhibitor
Organ Systems: endocrinemusculoskeletal
Mechanism of Action
Inhibits URAT1 and OAT4 transporters in the proximal tubule that normally reabsorb filtered urate, increasing urinary uric acid excretion (uricosuric action). Also inhibits renal secretion of various organic anions including penicillin (used therapeutically in some infection protocols).
URAT1 and other renal organic anion transporters (OAT)
Indications
- gout (chronic — to increase urate excretion)
- adjunct to penicillin therapy (to prolong penicillin levels by blocking renal secretion)
Contraindications
- uric acid nephrolithiasis or overproduction of urate
- CrCl <50 mL/min (ineffective)
- acute gout attack
Adverse Effects
Common
- GI upset
- headache
- rash
- increased uric acid stone risk
Serious
- nephrolithiasis (uric acid and other stones)
- hypersensitivity reactions
- hemolytic anemia (G6PD deficiency)
Pharmacokinetics (ADME)
| Absorption | oral; well absorbed; food reduces GI side effects |
| Distribution | 93–99% protein bound |
| Metabolism | hepatic metabolism to active and inactive metabolites |
| Excretion | renal |
| Half-life | 6–12 hours |
| Onset | days to weeks |
| Peak | 2–4 hours |
| Duration | continuous |
| Protein Binding | 93–99% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| penicillin | probenecid blocks renal secretion of penicillin, doubling or tripling levels; used clinically for gonorrhea and other infections | beneficial |
| NSAIDs (indomethacin, naproxen) | probenecid inhibits renal secretion of NSAIDs, increasing their levels | moderate |
| methotrexate | inhibition of renal transport increases methotrexate toxicity | major |
Nursing Considerations
- High fluid intake (2–3 L/day) is essential to prevent uric acid nepholithiasis; alkalinizing urine with sodium bicarbonate can further reduce stone risk.
- Contraindicated in patients who overproduce urate (24-hour urine uric acid >800 mg/day) — probenecid increases urinary urate, worsening stone risk in overproducers.
- Do NOT initiate during acute gout attack; provide colchicine/NSAID prophylaxis for 3–6 months to prevent flares.
- Requires adequate renal function (CrCl >50 mL/min) for effectiveness; ineffective in CKD.
Clinical Pearls
- Probenecid works only in gout patients who are underexcretors of uric acid (the majority of gout patients); it is ineffective and potentially harmful in overproducers, who need xanthine oxidase inhibitors instead.
- The penicillin interaction is clinically used: probenecid prolongs serum penicillin levels by blocking tubular secretion, enabling less frequent dosing in certain infections (historically used in gonorrhea therapy).
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.