Biotransformation of 4-dimethylaminophenol in man.

1) The biotransformation of 4-dimethylaminophenol (DMAP) was studied on six healthy male volunteers. After i.v. injection of 3.2 mg DMAP-HCl/kg the metabolites were analyzed in the 24 h urine with an isotope dilution technique. 2) For the isotope dilution technique the 14C-labeled metabolites were synthetized from 14C-DMAP. 14C-DMAP-glucuronide was produced in isolated hepatocytes and purified. 3) Two thirds of the DMAP applied were identified in the 24 h urine: 40% DMAP-glucuronide, 12% DMAP-sulfate, and 15% DMAP-thioethers. About 65% of the thioether fraction consisted of S,S,S-(2-dimethylamino-5-hydroxy-1,3,4-phenylene)tris-cysteine and 3% of the corresponding N-acetyl derivative. 4) As compared to dogs and rats humans produced more glucuronide at the expense of sulfate whereas thioether formation was equal in man and dog.