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.
D000120:Acecainide / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D000974:Antibodies, Antinuclear; D000917:Antibody Formation; D006801:Humans; D006898:Hydroxylamines / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced*; D051379:Mice; D010641:Phenotype; D011342:Procainamide / Q000009:adverse effects / Q000378:metabolism*; D013997:Time Factors
D000974:Antibodies, Antinuclear; D006898:Hydroxylamines; D000120:Acecainide; D011342:Procainamide