EVIDENCE FOR THE BIOTRANSFORMATION OF PROCAINAMIDE TO A REACTIVE METABOLITE

The antiarrhythmic drug procainamide formed reactive metabolites in the Salmonella typhimurium tester system. Further, procainamide covalently bound to mouse liver macromolecules. This binding was increased by phenobarbital pretreatment and decreased by SKF 525A pretreatment. In the presence of a mouse microsomal activating system, the reversion rate of tester strain TA100 was significantly increased by procainamide. This increase was dependent on the amount of microsomal protein and NADPH. Substitution on the aromatic amine antagonized the bioactivation of procainamide. N-Acetylprocainamide was 50% less active than procainamide. Removal of the aromatic amine of procainamide decreased reactivity. Procainamide is biotransformed by mouse liver microsomes to a reactive metabolite capable of interacting with nuclear macromolecules. Optimum bioactivation is dependent on a nonsubstituted arylamine. © 1979.