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 probenecid 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 significantly reduced, whereas that of paracetamol was unchanged. Probenecid was shown to be an uncompetitive inhibitor of paracetamol glucuronidation in vitro, using rat liver microsomes.
Kamali
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Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, UK.
D000082:Acetaminophen / Q000378:metabolism* / Q000493:pharmacokinetics*; D000328:Adult; D000818:Animals; D029681:Arabidopsis Proteins; D004347:Drug Interactions; D005260:Female; D005964:Glucosyltransferases / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology*; D051381:Rats
D029681:Arabidopsis Proteins; D000082:Acetaminophen; D005964:Glucosyltransferases; C457769:PRC1 protein, Arabidopsis; C028634:cellulose synthase (UDP-forming); D011339:Probenecid