Probenecid Paracetamol

Diflunisal Overdose (15 g) of diflunisal leads to poisoning, which could be fatal.51 Treatment can be given by gastric lavage and supportive care. Interactions of diflunisal with indomethacin, paracetamol, antacids, benzodiazepines, and probenecid have been reported.5 Concomitant use with indomethacin should be avoided, as this could cause fatal GI complications. 

Concomitant administration of paracetamol with other hepatotoxic drugs or drugs acting on liver microsomal enzymes enhances paracetamol toxicity. Other drugs that interact with paracetamol are metoclopramide, probenecid, and cholestyramine.81... 

F. Kamali, The effect of probenecid on paracetamol metabolism and pharmacokinetics. Eur. J. Clin. Pharmacol. 45 551-553, 1993. 

Tetraethylammonium Quinine Methadone Paracetamol Nitrofurantoin Choline A few vitamins Imipenem Probenecid... 

A metabolic study in 10 healthy subjects found that the 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 the urine stayed the same, but the glucuronide metabolite fell sharply. Another study in 11 subjects also found that probenecid 500 mg every 6 hours almost halved (from 329 to 178 mL/minute) the clearance of a 650-mg intravenous dose of paracetamol. The urinary excretion of the glucuronide metabolite was decreased by 68% and the excretion of the sulfate metabolite increased by 49%. These studies suggest that probenecid inhibits paracetamol glucuronida-tion, possibly by inhibiting glucuronyltransferase. See also paracetamol , (p.l33). The praetical consequences of this interaction are uncertain but there seem to be no adverse reports. 

Kamali F, Rawlins MD. Influence of probenecid and paracetamol (acetaminophen) on zidovudine glucuronidation in human liver in vitro. Biopharm Drug Dispos (1992) 13, 403-9. 

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