The implications of procainamide metabolism to its induction of lupus

The principal metabolic pathway of procainamide leads to formation of the less toxic N-acetyl-procainamide and the rapid acetylator phenotype is associated with a lower incidence of procainamide-induced lupus. Another metabolic pathway forms a reactive metabolite which causes revertants in the Ames test and covalently binds to microsomal protein. A study of the metabolism of procainamide revealed three metabolites that have not been previously described. A comparison of the metabolites of N-acetylprocainamide with those of procainamide suggests possibilities for the identity of the reactive metabolite. The hypotheses to be discussed explore the relationships between the formation of a reactive metabolite and the induction of lupus.