The effect of acetaminophen on the disposition of fenoldopam: Competition for sulfation

Abstract

Both fenoldopam and acetaminophen undergo conjugation with sulfate in humans. The present study was undertaken to determine if a metabolic interaction exists between these two compounds in humans. Twelve healthy male volunteers participated in a single-dose crossover study with 100 mg fenoldopam (capsule) alone or in combination with 1000 mg acetaminophen. The effects of chronic acetaminophen dosing (1000 mg three times/day for 7 days) on a single 100 mg tablet of fenoldopam were studied in a second crossover study in seven additional volunteers. Concomitant dosing with fenoldopam with acetaminophen resulted in increases in peak fenoldopam plasma concentration and AUC after both single (+32% and +50%, respectively) and chronic (+73% and +66%, respectively) acetaminophen dosing. Decreases in peak plasma concentrations and AUC for fenoldopam's sulfated metabolites were seen in both studies. These findings indicate a metabolic basis for the interaction between fenoldopam and acetaminophen, presumably through a competition for inorganic sulfate.