THE EFFECT OF PROBENECID ON PARACETAMOL METABOLISM AND PHARMACOKINETICS

The influence of probenecid on the pharmacokinetics of paracetamol was investigated in a group of healthy volunteers. Pretreatment with prob enecid caused a significant decrease in paracetamol clearance (6.23 to 3.42 ml . min-1 kg-1). The urinary excretion of paracetamol sulphate (243 to 193 mg); and paracetamol glucuronide (348 to 74.5 mg) were sig nificantly reduced, whereas that of paracetamol was unchanged. Probene cid was shown to be an uncompetitive inhibitor of paracetamol glucuron idation in vitro, using rat liver microsomes.