probenecid (Benemid, Probalan)

Introduction

Tradenames: Benemid, Probalan.

Indications

• treatment of gout, hyperuricemia
• NOT to be used for acute attacks of gout
• used to prolong action of penicillins & some, but not all cephalosporins

Contraindications

• history of renal stones (nephrolithiasis)
• ineffective in patients with renal failure
  • eGFR < 30-60 mL/min/1.73 m2

pregnancy category = b

safety in lactation = ?

Dosage

• gout:
  • 250 mg PO BID x 7 days, then 500 mg PO BID
  • start 500 mg PO QD
  • to prevent renal colic from uric acid stones, liberalize fluid intake & alkalinize urine with 3-7.5 g of NaHCO3 until urate levels normalize
  • use in conjunction with colchicine
• adjunct to penicillin injection:
  • adults: 1 g PO X 1
  • children 2-14 years: 25 mg/kg (initial), then 10 mg/kg QID

Tabs: 500 mg

Pharmacokinetics

• 74-99% bound to plasma proteins
• metabolized or conjugated
• elimination displays Michaelis-Menton elimination
• < 5% of drug is excreted unchanged

elimination via kidney

elimination via liver

Adverse effects

• common (> 10%)
  • gouty arthritis (acute), headache, anorexia, nausea/vomiting
• less common (1-10%)
  • dizziness, flushing of face, sore gums, rash, itching, urinary frequency & painful urination, renal calculi
• uncommon (< 1%)
  • urate nephropathy, nephrotic syndrome, leukopenia, hepatic necrosis, hemolytic anemia, aplastic anemia, anaphylaxis

• drug adverse effects of sulfonamides

Drug interactions

• salicylates block uricosuric effect of probenecid
• acyclovir, dapsone, methotrexate, NSAIDs, rifampin, sulfonamides, zidovudine levels are increased by probenecid
• benzodiazepines have a faster onset & prolonged effect
• allopurinol is synergistic with probenecid in lowering uric acid

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Mechanism of action

• inhibits renal tubular resorption of urate, increasing urate elimination
• inhibits tubular excretion of many antibiotics
• inhihits OAT3, which is used by viruses including SARS-CoV2, influenza & RSV to transport & package viral proteins in infected cells.

Comparative biology

• probenecid inhibits replication of SARS-CoV2, influenza & RSV in animal models & human lung cells

More general terms

• sulfonamide
• uricosuric agent

Component of

• colchicine/probenecid (ColBENEMID)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4911
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=32095