Probenecid is an inhibitor of CYP2C9 and CYP1A2, but is not listed as a mechanism-based inhibitor. No induction of any major CYP enzymes has been described. Risk for gastrointestinal adverse events in the form of nausea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Di-propyl sulphonamoyl benzoic acid. M= 285. Practically insoluble in water.

Probenecid is indicated for the treatment of arthritis urica. Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack is nausea.

Probenecid is extensively metabolised by glucuronide conjugation and by oxidation of the alkyl side chains (Cunningham 1981). The half-life elimination is 4-12 hours and is dose-dependent (Cunningham 1981). Probenecid demonstrated no response in activation of PXR (Luo 2002 and Sinz 2006) and did not induce CYP3A4 in vitro (Luo 2002). When probenecid was co-administrated with carbamazepine (a CYP3A4 and CYP2C8 substrate) the AUC of carabamazepine decreased by 19%. This could indicate that probenecid might be an inducer of CYP3A4 or CYP2C8, or both of them (Cui 2008 and Kim 2005). The decrease in AUC is however, according to the U.S Food and Drug administration, too low for probenecid to considered as an inducer (FDA). Besides, carbamazepine is listed as an inducer of CYP3A4 (Hisaka 2010 and Pelkonen 2008), which means that there is a possibility that carbamazepine induced its own metabolism. It is listed as an inhibitor of CYP2C9 (Cheng 2010 and Flockhart 2007). A clinical study showed that co-administration of probenecid with naproxen reduced the clearance of naproxen conjugates and increased the excretion of desmethylnaproxen. The formation of desmethylnaproxen is the favoured pathway when renal clearance and conjugation of naproxen are inhibited. It does not have the same capacity as the usual pathway with the result that the half-life elimination and AUC increases (Runkel 1978). Naproxen is metabolised by CYP1A2 and CYP2C9 (Norsk Legemiddelhåndbok), and the data might therefore indicate that probenecid inhibit CYP1A2 or CYP2C9, or both.

Probenecid has shown conflicting results of porphyrinogenicity in vitro (Disler 1982, Moore 1997 and Rifkind 1976).