Paracetamol (Acetaminophen) + Probenecid - Drug Interactions

Probenecid reduces clearance of paracetamol

Clinical evidence,mechanism, importance and management

A metabolic study in 10 healthy subjects found that clearance of paracetamol 1.5 g was almost halved (from 6.23 to 3.42 mL/minute per kg) when it was taken 1 hour after a 1-g dose of probenecid. The amount of unchanged paracetamol in urine stayed same, but glucuronide metabolite fell sharply (See reference number 1). Another study in 11 subjects also found that probenecid 500mg every 6 hrs almost halved (from 329 to 178 mL/minute) clearance of a 650mg intravenous dose of paracetamol. The urinary excretion of glucuronide metabolite was decreased by 68 % and excretion of sulfate metabolite increased by 49 % (See reference number 2). These studies suggest that probenecid inhibits paracetamol glucuronidation,possibly by inhibiting glucuronyltransferase. See also paracetamol,. The practical consequences of this interaction are uncertain but there seem to be no adverse reports.

Kamali F. The effect of probenecid on paracetamol metabolism and pharmacokinetics. Eur J Clin Pharmacol (1993) 45,551–3.

Abernethy DR,Greenblatt DJ, Ameer B, Shader RI. Probenecid impairment of acetaminophenand lorazepam clearance: direct inhibition of ether glucuronide formation. J Pharmacol Exp Ther (1985) 234, 345–9.