Pharmacology · Other antigout agents
Probenecid !
A uricosuric tablet that makes the kidneys pass more uric acid. It also keeps penicillin in the blood longer.
Updated 2026-11-01
The figure shows human OAT1 (SLC22A6) with probenecid bound; OAT1 belongs to the same transporter family as URAT1 and explains the penicillin and methotrexate interactions.
Mechanism of action
In the proximal tubule probenecid blocks urate reabsorption, mainly through URAT1, so more uric acid leaves in the urine and serum urate falls. It also blocks the organic anion transporters that secrete many acidic drugs into the urine, which raises the levels of penicillins, methotrexate and others.
- Blocks URAT1 in the proximal tubule
- Less urate is reabsorbed
- More uric acid in the urine; serum urate falls
- Also slows secretion of acidic drugs
Pharmacokinetics
- Absorption
- Oral
- Elimination
- Works only while the kidneys filter well enough
Indications
- Hyperuricaemia of gout Gout →
- Adjunct to raise and prolong penicillin levels
Adverse effects
Common
- Headache
- Loss of appetite, nausea, vomiting
- Gout flares at the start
Contraindications
- Hypersensitivity to probenecid
- Children under 2 years of age
- Known uric acid kidney stones or blood dyscrasias (not recommended)
- Starting during an acute gout attack
Key interactions
- Salicylates (aspirin)
- Cancel its uricosuric effect; contraindicated in people taking probenecid.
- Penicillins
- Their tubular secretion falls and blood levels rise (used on purpose in some infections).
- Methotrexate
- Levels and toxicity rise; methotrexate is reduced and levels may be monitored.
What is monitored
- Serum uric acid
- Kidney function
- Signs of kidney stones (flank pain, blood in the urine)
Administration and safety
- Oral tablet.
- Plenty of fluids, and sometimes alkalinising the urine, help prevent uric acid stones.
- A combined tablet with colchicine exists; the product is checked.
Nursing care
- Encourage a generous fluid intake unless restricted.
- Teach to avoid aspirin and products with salicylates; paracetamol is preferred for mild pain.
- Teach to report flank pain or blood in the urine.
- Check that the gout flare has settled before the first dose.
Pregnancy and breastfeeding
It crosses the placenta; it is used in pregnancy only when the treating team judges it needed.
Test yourself
Think of the answer, then tap the question to see it.
How does probenecid lower uric acid?
It blocks urate reabsorption in the proximal tubule (mainly URAT1), so more uric acid is excreted.
Why is probenecid avoided in people with uric acid kidney stones?
It increases uric acid in the urine, which can form more stones.
Why has probenecid been given together with penicillin?
It blocks the tubular secretion of penicillin, raising and prolonging its blood levels.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Probenecid: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); DailyMed - PROBENECID tablet (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 42 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.